6o5n - Revision history

OCA at 14:50, 13 March 2024

OCA — Wed, 13 Mar 2024 14:50:35 GMT

←Older revision		Revision as of 14:50, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6o5n' size='340' side='right'caption='[[6o5n]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='6o5n' size='340' side='right'caption='[[6o5n]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o5n]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Chick Chick~~], [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5N OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6O5N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o5n]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5N FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QW9:[2-(4-methyl-1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>QW9</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.003Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o5m\|6o5m]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QW9:[2-(4-methyl-1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>QW9</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">STMN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6o5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5n OCA], [https://pdbe.org/6o5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5n RCSB], [https://www.ebi.ac.uk/pdbsum/6o5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5n ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6o5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5n OCA], [~~http~~://pdbe.org/6o5n PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6o5n RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6o5n PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5n ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [[http://www.uniprot.org/uniprot/STMN4_HUMAN STMN4_HUMAN]] Exhibits microtubule-destabilizing activity. [[http://www.uniprot.org/uniprot/A0A287AGU7_PIG A0A287AGU7_PIG]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.[RuleBase:RU000352][SAAS:SAAS00031082]	+	[https://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship (SAR) studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogs, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogs disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analog 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models, but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.	+

-	~~Structure guided design, synthesis, and biological evaluation of 2-(1H-Indol-3-yl)-1H-imidazol~~-4-~~yl)(3,~~4,5-trimethoxyphenyl) Methanone (ABI-231) analogs targeting the colchicine binding site in tubulin.,Wang Q, Arnst K, Wang Y, Kumar GK, Ma D, White SW, Miller DD, Li W, Li W J Med Chem. 2019 Jun 28. doi: 10.1021/acs.jmedchem.9b00706. PMID:31251599<ref>PMID:31251599</ref>	+	==See Also==
-		+	*[[Stathmin-4 3D structures\|Stathmin-4 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+	*[[Tubulin 3D Structures\|Tubulin 3D Structures]]
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6o5n" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Chick~~]]	+	[[Category: Gallus gallus]]
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sus scrofa]]		[[Category: Sus scrofa]]
-	[[Category: Kumar, G]]	+	[[Category: Kumar G]]
-	[[Category: Li, W]]	+	[[Category: Li W]]
-	[[Category: Wang, Y]]	+	[[Category: Wang Y]]
-	[[Category: White~~, S W]]~~	+	[[Category: White SW]]
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Colchicine]]~~	+
-	~~[[Category: Microtubule inhibitor~~]]	+

OCA at 07:01, 31 July 2019

OCA — Wed, 31 Jul 2019 07:01:18 GMT

←Older revision		Revision as of 07:01, 31 July 2019
Line 3:		Line 3:
	<StructureSection load='6o5n' size='340' side='right'caption='[[6o5n]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='6o5n' size='340' side='right'caption='[[6o5n]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o5n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O5N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o5n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick], [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O5N FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QW9:[2-(4-methyl-1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>QW9</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QW9:[2-(4-methyl-1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>QW9</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o5m\|6o5m]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o5m\|6o5m]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">STMN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5n OCA], [http://pdbe.org/6o5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5n RCSB], [http://www.ebi.ac.uk/pdbsum/6o5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5n ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5n OCA], [http://pdbe.org/6o5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5n RCSB], [http://www.ebi.ac.uk/pdbsum/6o5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5n ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Chick]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sus scrofa]]		[[Category: Sus scrofa]]

OCA at 05:49, 10 July 2019

OCA — Wed, 10 Jul 2019 05:49:36 GMT

←Older revision		Revision as of 05:49, 10 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6o5n is ~~ON HOLD~~	+	==Tubulin-RB3_SLD-TTL in complex with compound 10ab==
		+	<StructureSection load='6o5n' size='340' side='right'caption='[[6o5n]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6o5n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O5N FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QW9:[2-(4-methyl-1H-indol-3-yl)-1H-imidazol-5-yl](3,4,5-trimethoxyphenyl)methanone'>QW9</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o5m\|6o5m]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5n OCA], [http://pdbe.org/6o5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5n RCSB], [http://www.ebi.ac.uk/pdbsum/6o5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5n ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [[http://www.uniprot.org/uniprot/STMN4_HUMAN STMN4_HUMAN]] Exhibits microtubule-destabilizing activity. [[http://www.uniprot.org/uniprot/A0A287AGU7_PIG A0A287AGU7_PIG]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.[RuleBase:RU000352][SAAS:SAAS00031082]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship (SAR) studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogs, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogs disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analog 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models, but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.

-	~~Authors: Kumar~~, G., Wang, Y., Li, W., White, S.W.	+	Structure guided design, synthesis, and biological evaluation of 2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) analogs targeting the colchicine binding site in tubulin.,Wang Q, Arnst K, Wang Y, Kumar GK, Ma D, White SW, Miller DD, Li W, Li W J Med Chem. 2019 Jun 28. doi: 10.1021/acs.jmedchem.9b00706. PMID:31251599<ref>PMID:31251599</ref>

-	~~Description: Tubulin~~-~~RB3_SLD~~-~~TTL in complex with compound 10ab~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Wang, Y]]~~	+	<div class="pdbe-citations 6o5n" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Li, W~~]]	+	== References ==
-	[[Category: ~~White, S.W~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Sus scrofa]]
	[[Category: Kumar, G]]		[[Category: Kumar, G]]
		+	[[Category: Li, W]]
		+	[[Category: Wang, Y]]
		+	[[Category: White, S W]]
		+	[[Category: Cancer]]
		+	[[Category: Cell cycle]]
		+	[[Category: Colchicine]]
		+	[[Category: Microtubule inhibitor]]

OCA: Protected "6o5n" [edit=sysop:move=sysop]

OCA — Wed, 13 Mar 2019 10:14:41 GMT

Protected "6o5n" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:14, 13 March 2019

OCA: New page: '''Unreleased structure''' The entry 6o5n is ON HOLD Authors: Kumar, G., Wang, Y., Li, W., White, S.W. Description: Tubulin-RB3_SLD-TTL in complex with compound 10ab [[Category: Unrele...

OCA — Wed, 13 Mar 2019 10:14:40 GMT

New page: '''Unreleased structure''' The entry 6o5n is ON HOLD Authors: Kumar, G., Wang, Y., Li, W., White, S.W. Description: Tubulin-RB3_SLD-TTL in complex with compound 10ab [[Category: Unrele...

New page

'''Unreleased structure'''

The entry 6o5n is ON HOLD

Authors: Kumar, G., Wang, Y., Li, W., White, S.W.

Description: Tubulin-RB3_SLD-TTL in complex with compound 10ab
[[Category: Unreleased Structures]]
[[Category: Wang, Y]]
[[Category: Li, W]]
[[Category: White, S.W]]
[[Category: Kumar, G]]