Sandbox Reserved 1613 - Revision history

http://52.214.119.220/wiki/index.php?action=history&feed=atom&title=Sandbox_Reserved_1613 Sandbox Reserved 1613 - Revision history 2026-04-04T15:56:54Z Revision history for this page on the wiki MediaWiki 1.11.2 http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195433&oldid=prev Shelby Skaggs at 13:56, 21 April 2020 2020-04-21T13:56:49Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:56, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 17:</td> <td colspan="2" class="diff-lineno">Line 17:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name="Taylor">PMID:28554189</ref> Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name="Taylor">PMID:28554189</ref> Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.<ref name="Manolaridis" /> <ref name="Jackson">PMID:29610494</ref></div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><ref name="Manolaridis" /></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div></div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><ref name="Jackson">PMID:29610494</ref></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2" class="diff-lineno">Line 26:</td> <td colspan="2" class="diff-lineno">Line 24:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules. ABCG2 is found in multiple biological membranes, especially at blood barriers such as the <del style="color: red; font-weight: bold; text-decoration: none;">blood-</del>brain barrier <del style="color: red; font-weight: bold; text-decoration: none;">(BBB)</del>, <del style="color: red; font-weight: bold; text-decoration: none;">blood-</del>testis barrier, and the blood-placental barrier. The prevalence of ABCG2 protects those tissues from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates.<ref name="Fetsch">PMID:15990223</ref></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules.<ins style="color: red; font-weight: bold; text-decoration: none;"><ref name="Jackson">PMID:29610494</ref> </ins>ABCG2 is found in multiple biological membranes, especially at blood barriers such as the <ins style="color: red; font-weight: bold; text-decoration: none;">[https://en.wikipedia.org/wiki/Blood </ins>brain barrier<ins style="color: red; font-weight: bold; text-decoration: none;">]</ins>, <ins style="color: red; font-weight: bold; text-decoration: none;">[https://en.wikipedia.org/wiki/Blood </ins>testis barrier<ins style="color: red; font-weight: bold; text-decoration: none;">]</ins>, and the blood-placental barrier. The prevalence of ABCG2 protects those tissues from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates.<ref name="Fetsch">PMID:15990223</ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195432&oldid=prev Shelby Skaggs at 13:47, 21 April 2020 2020-04-21T13:47:26Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:47, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 26:</td> <td colspan="2" class="diff-lineno">Line 26:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules. <del style="color: red; font-weight: bold; text-decoration: none;">It </del>is found in <del style="color: red; font-weight: bold; text-decoration: none;">different </del>biological membranes, such as the blood-brain barrier (BBB), blood-testis barrier, and the blood-placental barrier. <del style="color: red; font-weight: bold; text-decoration: none;">It is thought to help protect </del>those tissues <del style="color: red; font-weight: bold; text-decoration: none;">and many others </del>from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates.<ref name="Fetsch">PMID:15990223</ref></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules. <ins style="color: red; font-weight: bold; text-decoration: none;">ABCG2 </ins>is found in <ins style="color: red; font-weight: bold; text-decoration: none;">multiple </ins>biological membranes, <ins style="color: red; font-weight: bold; text-decoration: none;">especially at blood barriers </ins>such as the blood-brain barrier (BBB), blood-testis barrier, and the blood-placental barrier. <ins style="color: red; font-weight: bold; text-decoration: none;">The prevalence of ABCG2 protects </ins>those tissues <ins style="color: red; font-weight: bold; text-decoration: none;"> </ins>from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates.<ref name="Fetsch">PMID:15990223</ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195431&oldid=prev Shelby Skaggs at 13:42, 21 April 2020 2020-04-21T13:42:16Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:42, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 26:</td> <td colspan="2" class="diff-lineno">Line 26:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Function==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules. It is found in different biological membranes, such as the blood-brain barrier (BBB), blood-testis barrier, and the blood-placental barrier. It is thought to help protect those tissues and many others from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>ABCG2 transports a variety of <scene name='83/832939/Mz29/1'>substrates</scene>, particularly flat, hydrophobic, and/or polycylcic molecules. It is found in different biological membranes, such as the blood-brain barrier (BBB), blood-testis barrier, and the blood-placental barrier. It is thought to help protect those tissues and many others from cytotoxins. In addition to cytotoxin protection, ABCG2 secretes endogenous substrates in the adrenal gland, excretes toxins in the liver and kidneys, and regulates absorption of substrates.<ref name="Fetsch">PMID:15990223</ref></div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><ref name="Fetsch">PMID:15990223</ref></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Fab-5D3===</div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195430&oldid=prev Jaelyn M. Voyles at 13:37, 21 April 2020 2020-04-21T13:37:19Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:37, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 15:</td> <td colspan="2" class="diff-lineno">Line 15:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name="Taylor">PMID:28554189</> Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name="Taylor">PMID:28554189</<ins style="color: red; font-weight: bold; text-decoration: none;">ref</ins>> Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><ref name="Manolaridis"<del style="color: red; font-weight: bold; text-decoration: none;">>PMID:30405239<</del>/<del style="color: red; font-weight: bold; text-decoration: none;">ref</del>></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ref name="Manolaridis" /></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><ref name="Jackson">PMID:29610494</ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><ref name="Jackson">PMID:29610494</ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Jaelyn M. Voyles http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195429&oldid=prev Shelby Skaggs at 13:33, 21 April 2020 2020-04-21T13:33:36Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:33, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 15:</td> <td colspan="2" class="diff-lineno">Line 15:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name=" Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ref name="<ins style="color: red; font-weight: bold; text-decoration: none;">Taylor">PMID:28554189</> </ins>Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195427&oldid=prev Shelby Skaggs at 13:28, 21 April 2020 2020-04-21T13:28:16Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:28, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 2:</td> <td colspan="2" class="diff-lineno">Line 2:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:ABCG2 DimerPic NoWatermark.png|400 px|right|thumb|Figure 1: Multidrug-transporter ABCG2 is a dimer.]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:ABCG2 DimerPic NoWatermark.png|400 px|right|thumb|Figure 1: Multidrug-transporter ABCG2 is a dimer <ins style="color: red; font-weight: bold; text-decoration: none;">(6ffc)</ins>.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells.<ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells.<ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2" class="diff-lineno">Line 15:</td> <td colspan="2" class="diff-lineno">Line 15:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 2: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2.<ins style="color: red; font-weight: bold; text-decoration: none;"><ref name=" </ins>Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195426&oldid=prev Shelby Skaggs at 13:19, 21 April 2020 2020-04-21T13:19:28Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:19, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 2:</td> <td colspan="2" class="diff-lineno">Line 2:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:ABCG2 DimerPic NoWatermark.png|400 px|right|thumb|Figure 1: Multidrug-transporter ABCG2 is a dimer.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells.<ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells.<ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2" class="diff-lineno">Line 12:</td> <td colspan="2" class="diff-lineno">Line 13:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 protein is comprised of a [https://en.wikipedia.org/wiki/Molecular_diffusion homodimer] which each have two specific domains: one spanning the cell membrane and one involved with nucleotide [https://en.wikipedia.org/wiki/Ligand_(biochemistry) binding]. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABCG2 protein is comprised of a [https://en.wikipedia.org/wiki/Molecular_diffusion homodimer] which each have two specific domains: one spanning the cell membrane and one involved with nucleotide [https://en.wikipedia.org/wiki/Ligand_(biochemistry) binding]. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Mechanism of Substrate Transport ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Mechanism of Substrate Transport ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure <del style="color: red; font-weight: bold; text-decoration: none;">1</del>: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure <ins style="color: red; font-weight: bold; text-decoration: none;">2</ins>: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates.<ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> </table>

Shelby Skaggs http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195421&oldid=prev Jaelyn M. Voyles at 13:14, 21 April 2020 2020-04-21T13:14:52Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 13:14, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 17:</td> <td colspan="2" class="diff-lineno">Line 17:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><ref name="Jackson">PMID:29610494</ref></div></td><td colspan="2"> </td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><ref name="Manolaridis">PMID:30405239</ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><ref name="Manolaridis">PMID:30405239</ref></div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ref name="Jackson">PMID:29610494</ref></div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Transmembrane Domain Stabilization===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Transmembrane Domain Stabilization===</div></td></tr> <tr><td colspan="2" class="diff-lineno">Line 34:</td> <td colspan="2" class="diff-lineno">Line 35:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Disease ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Disease ==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One of the causes for multidrug resistant cancers is the excretion of cancer drugs out of the cell, thereby decreasing the effective intracellular concentration. ABCG2, also known as the breast cancer resistance protein (BCRP), effluxes multiple chemotherapeutic agents such as [https://en.wikipedia.org/wiki/Mitoxantrone mitoxantrone] and [https://en.wikipedia.org/wiki/Camptothecin camptothecin] analogies, making the cancerous breast cells resistant to chemotherapy. Competitive inhibitors, such as <scene name='83/832939/Abcg2_bound_to_mz29/3'>MZ29</scene>, shut down ABCG2 to stop the efflux of cancer drugs in order to combat the resistivity of breast cancer. <ref name="Jackson" /<del style="color: red; font-weight: bold; text-decoration: none;">> <ref>[ https://en.wikipedia.org/wiki/ABCG2 "ABCG2 -." Wikipedia, the Free Encyclopedia. Web. 20 Apr. 2020].</ref</del>></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One of the causes for multidrug resistant cancers is the excretion of cancer drugs out of the cell, thereby decreasing the effective intracellular concentration. ABCG2, also known as the breast cancer resistance protein (BCRP), effluxes multiple chemotherapeutic agents such as [https://en.wikipedia.org/wiki/Mitoxantrone mitoxantrone] and [https://en.wikipedia.org/wiki/Camptothecin camptothecin] analogies, making the cancerous breast cells resistant to chemotherapy. Competitive inhibitors, such as <scene name='83/832939/Abcg2_bound_to_mz29/3'>MZ29</scene>, shut down ABCG2 to stop the efflux of cancer drugs in order to combat the resistivity of breast cancer. <ref name="Jackson" /></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABC transporter family has been found as a prevalent piece of multi-drug resistant cancers and therefore became a popular target towards inhibition. Three generations of drugs were made in order to inhibit a similar protein from the same family, ABCC1 at its interior binding site including cyclosporine A (first generation), valspodar (second generation), and Elacridar (3rd generation). Importantly, cyclosporine A and Elacridar were found to inhibit both ABCC1 and ABCG2 and in one trial had success along with chemotherapy in the treatment of acute myeloid leukemia but because of either side effects or experimentation that was not able to be duplicated, this research was mostly shelved. The main issue in their failure to find a drug to inhibit this protein was the failure to develop a high-resolution structure of this protein with the technology available at the time of this drug development. Now, with high resolution images of the structures, fourth generation inhibitors are being developed with more success in inhibition without additional drug interactions or cell toxicity. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The ABC transporter family has been found as a prevalent piece of multi-drug resistant cancers and therefore became a popular target towards inhibition. Three generations of drugs were made in order to inhibit a similar protein from the same family, ABCC1 at its interior binding site including cyclosporine A (first generation), valspodar (second generation), and Elacridar (3rd generation). Importantly, cyclosporine A and Elacridar were found to inhibit both ABCC1 and ABCG2 and in one trial had success along with chemotherapy in the treatment of acute myeloid leukemia but because of either side effects or experimentation that was not able to be duplicated, this research was mostly shelved. The main issue in their failure to find a drug to inhibit this protein was the failure to develop a high-resolution structure of this protein with the technology available at the time of this drug development. Now, with high resolution images of the structures, fourth generation inhibitors are being developed with more success in inhibition without additional drug interactions or cell toxicity. </div></td></tr> </table>

Jaelyn M. Voyles http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195387&oldid=prev Jaelyn M. Voyles at 11:11, 21 April 2020 2020-04-21T11:11:25Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 11:11, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 2:</td> <td colspan="2" class="diff-lineno">Line 2:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='6ffc' size='350' frame='true' side='right' caption='Figure 1: ABCG2 6FFC' scene=’’></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Introduction==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells<ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>The ABCG2 transporter protein is a notable [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane protein]. It transports [https://en.wikipedia.org/wiki/Xenobiotic xenobiotic] material out of cells in many tissues. ABCG2 belongs to the family of 48 transporter proteins called ATP-binding cassette transporters (ABC transporters). The ABC transporters differ from each other by their size structure, and ordering of domains. Ample evidence has shown a link between [https://en.wikipedia.org/wiki/Multiple_drug_resistance multi-drug resistance] and the presence of ABC transporters in the plasma membrane of cells. This is important as multi-drug resistance is one of the major indicators of bad prognoses in cancer treatment. In fact, 19 of the 48 transporters of the ABC family have been shown to transport [https://en.wikipedia.org/wiki/List_of_chemotherapeutic_agents chemotherapeutic agents] out of cells<ins style="color: red; font-weight: bold; text-decoration: none;">.</ins><ref name="Robey">PMID:29643473</ref> In recent studies, with [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electronic microscopy] (Cryo EM), the unique <scene name='83/832939/2_cavities/1'>two cavity substrate transport structure</scene>, inward facing nucleotide binding domain and <scene name='83/832939/El-3/3'>condensed EL-3 structure</scene> of ABCG2 have been elucidated, among other features. These new discoveries have allowed for progress towards discovering the exact link between cancer and the ABC transporter family and have allowed for more effective drug treatment of cancer. This page will focus on the family of ABC transporters before delving into unique structural features of ABCG2 and finally describing the effects of this transporter on anti-cancer treatment.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==ABC Transporter Family==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==ABC Transporter Family==</div></td></tr> </table>

Jaelyn M. Voyles http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1613&diff=3195386&oldid=prev Jaelyn M. Voyles at 11:10, 21 April 2020 2020-04-21T11:10:55Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 11:10, 21 April 2020</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 5:</td> <td colspan="2" class="diff-lineno">Line 5:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==ABC Transporter Family==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==ABC Transporter Family==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>In the 1990's, [https://en.wikipedia.org/wiki/ATP-binding_cassette_transporter ABC binding cassette transporters] became the subject of much discussion as many were found to have links to the inhibition of [https://en.wikipedia.org/wiki/Molecular_diffusion anti-cancer therapies]. All 48 members of the family were studied and several structural aspects were found to be important to the characterization of [https://en.wikipedia.org/wiki/Transport_protein transporters] in this family. The first was the presence of two [https://en.wikipedia.org/wiki/Nucleotide nucleotide] binding [https://en.wikipedia.org/wiki/Protein_domain domains] (NBD) located in the cytoplasm of all cells which bound and [https://en.wikipedia.org/wiki/Hydrolysis hydrolyzed] [https://en.wikipedia.org/wiki/Adenosine_triphosphate ATP], providing the necessary energy for [https://en.wikipedia.org/wiki/Membrane_transport transport] of the [https://en.wikipedia.org/wiki/Substrate_(chemistry) substrate] to occur. In all 7 subfamilies (A-G) of the ABC family, the NBD's are greatly conserved.<ref name="Robey">PMID:29643473</ref><del style="color: red; font-weight: bold; text-decoration: none;">. </del>Each transporter of this family is made unique by the structure and form of their specific transmembrane binding domain (TMD). Each of the 48 transporters have 2 transmembrane domains which work to recognize and transport the substrates across the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] and out of the cell. The [https://en.wikipedia.org/wiki/Amino_acid residues] in the TMD provide the transporters each with specific substrates which they can transport. They also allow for the coupling of transport with [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] to transport molecules regardless of the [https://en.wikipedia.org/wiki/Molecular_diffusion concentration gradient]. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>In the 1990's, [https://en.wikipedia.org/wiki/ATP-binding_cassette_transporter ABC binding cassette transporters] became the subject of much discussion as many were found to have links to the inhibition of [https://en.wikipedia.org/wiki/Molecular_diffusion anti-cancer therapies]. All 48 members of the family were studied and several structural aspects were found to be important to the characterization of [https://en.wikipedia.org/wiki/Transport_protein transporters] in this family. The first was the presence of two [https://en.wikipedia.org/wiki/Nucleotide nucleotide] binding [https://en.wikipedia.org/wiki/Protein_domain domains] (NBD) located in the cytoplasm of all cells which bound and [https://en.wikipedia.org/wiki/Hydrolysis hydrolyzed] [https://en.wikipedia.org/wiki/Adenosine_triphosphate ATP], providing the necessary energy for [https://en.wikipedia.org/wiki/Membrane_transport transport] of the [https://en.wikipedia.org/wiki/Substrate_(chemistry) substrate] to occur. In all 7 subfamilies (A-G) of the ABC family, the NBD's are greatly conserved.<ref name="Robey">PMID:29643473</ref> Each transporter of this family is made unique by the structure and form of their specific transmembrane binding domain (TMD). Each of the 48 transporters have 2 transmembrane domains which work to recognize and transport the substrates across the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] and out of the cell. The [https://en.wikipedia.org/wiki/Amino_acid residues] in the TMD provide the transporters each with specific substrates which they can transport. They also allow for the coupling of transport with [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] to transport molecules regardless of the [https://en.wikipedia.org/wiki/Molecular_diffusion concentration gradient]. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Specific Members of the Family===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Specific Members of the Family===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>As previously mentioned, 19 of the 48 members of the transporter family are involved in chemotherapeutic removal from the cell. Of these, three, <scene name='83/832939/Abcb1/1'>ABCB1</scene>, ABCG2 and <scene name='83/832939/Abcc1/1'>ABCC1</scene> were identified for further study and comparison of [https://en.wikipedia.org/wiki/Chemical_structure structure] due to their function as multi-drug transporters<ref name="Robey">PMID:29643473</ref><del style="color: red; font-weight: bold; text-decoration: none;">. </del>The differences in their structures provided valuable information for scientific research into their substrate binding processes.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>As previously mentioned, 19 of the 48 members of the transporter family are involved in chemotherapeutic removal from the cell. Of these, three, <scene name='83/832939/Abcb1/1'>ABCB1</scene>, ABCG2 and <scene name='83/832939/Abcc1/1'>ABCC1</scene> were identified for further study and comparison of [https://en.wikipedia.org/wiki/Chemical_structure structure] due to their function as multi-drug transporters<ins style="color: red; font-weight: bold; text-decoration: none;">.</ins><ref name="Robey">PMID:29643473</ref> The differences in their structures provided valuable information for scientific research into their substrate binding processes.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==General Structure==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==General Structure==</div></td></tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 1: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 1: MZ29 bound to cavity 1 of ABCG2 (6ffc). Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates<ref name="Manolaridis">PMID:30405239</ref><del style="color: red; font-weight: bold; text-decoration: none;">. </del>Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Multidrug Transporter ABCG2 is a <scene name='83/832937/Dimer/1'>dimer</scene> that consists of two [https://en.wikipedia.org/wiki/Cavity cavities] separated by a <scene name='83/832937/Leucine_plug/4'>leucine plug</scene>. Cavity 1 is a binding pocket open to the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm] and the inner leaflet of the plasma membrane. Its shape is suitable to bind flat, hydrophobic and polycyclic substrates<ins style="color: red; font-weight: bold; text-decoration: none;">.</ins><ref name="Manolaridis">PMID:30405239</ref> Many of its amino acids residues form hydrophobic interactions with the bound substrate, as shown in green in '''Figure 1'''. Cavity 2 is located above the leucine plug. It is empty until a <scene name='83/832937/Atp_and_mg_bound_to_abcg2/4'>magnesium ion and ATP</scene> are bound to ABCG2. Its <scene name='83/832937/Cysteine_disulfide_bridges/5'>inter- and intra-disulfides</scene> (yellow is inter- and intra-molecular disulfides, golden is intra-molecular only) promote the release of the substrate from the cavity into the extracellular space. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One interesting feature of the NBD's is the fact that they remain in contact with one another even without a bound substrate. This makes the ABCG2 transporter unique and provides greater substrate specificity as the entrance to the transporter is not as globular as either ABCB1 or ABCC1. The entrance from the cytoplasm to the transporter is a [https://en.wikipedia.org/wiki/Hydrophobe hydrophobic] membrane entrance lined by <scene name='83/832939/Lining_of_entrance_of_nbd/1'>residues A397, V401, L405, L539, I543 and T547</scene> in both [https://en.wikipedia.org/wiki/Monomer monomers].</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Dimerization of ABCG2 was originally thought to be achieved with the help of the <scene name='83/832939/Disproved_dimerization_process/1'>406xxx410 structural motif</scene> in each of the two domains but Cryo-EM showed that the [https://en.wikipedia.org/wiki/Sequence_motif motifs] were on opposite sides of the protein.</div></td></tr> </table>

Jaelyn M. Voyles