2hyd
From Proteopedia
(New page: 200px<br /><applet load="2hyd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hyd, resolution 3.0Å" /> '''Multidrug ABC transpo...) |
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| - | [[Image:2hyd.gif|left|200px]]<br /><applet load="2hyd" size=" | + | [[Image:2hyd.gif|left|200px]]<br /><applet load="2hyd" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2hyd, resolution 3.0Å" /> | caption="2hyd, resolution 3.0Å" /> | ||
'''Multidrug ABC transporter SAV1866'''<br /> | '''Multidrug ABC transporter SAV1866'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Multidrug transporters of the ABC family facilitate the export of diverse | + | Multidrug transporters of the ABC family facilitate the export of diverse cytotoxic drugs across cell membranes. This is clinically relevant, as tumour cells may become resistant to agents used in chemotherapy. To understand the molecular basis of this process, we have determined the 3.0 A crystal structure of a bacterial ABC transporter (Sav1866) from Staphylococcus aureus. The homodimeric protein consists of 12 transmembrane helices in an arrangement that is consistent with cross-linking studies and electron microscopic imaging of the human multidrug resistance protein MDR1, but critically different from that reported for the bacterial lipid flippase MsbA. The observed, outward-facing conformation reflects the ATP-bound state, with the two nucleotide-binding domains in close contact and the two transmembrane domains forming a central cavity--presumably the drug translocation pathway--that is shielded from the inner leaflet of the lipid bilayer and from the cytoplasm, but exposed to the outer leaflet and the extracellular space. |
==About this Structure== | ==About this Structure== | ||
| - | 2HYD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with NA and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2HYD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HYD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Dawson, R | + | [[Category: Dawson, R J.P.]] |
| - | [[Category: Locher, K | + | [[Category: Locher, K P.]] |
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: NA]] | [[Category: NA]] | ||
[[Category: transport protein]] | [[Category: transport protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:47:06 2008'' |
Revision as of 15:47, 21 February 2008
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Multidrug ABC transporter SAV1866
Overview
Multidrug transporters of the ABC family facilitate the export of diverse cytotoxic drugs across cell membranes. This is clinically relevant, as tumour cells may become resistant to agents used in chemotherapy. To understand the molecular basis of this process, we have determined the 3.0 A crystal structure of a bacterial ABC transporter (Sav1866) from Staphylococcus aureus. The homodimeric protein consists of 12 transmembrane helices in an arrangement that is consistent with cross-linking studies and electron microscopic imaging of the human multidrug resistance protein MDR1, but critically different from that reported for the bacterial lipid flippase MsbA. The observed, outward-facing conformation reflects the ATP-bound state, with the two nucleotide-binding domains in close contact and the two transmembrane domains forming a central cavity--presumably the drug translocation pathway--that is shielded from the inner leaflet of the lipid bilayer and from the cytoplasm, but exposed to the outer leaflet and the extracellular space.
About this Structure
2HYD is a Single protein structure of sequence from Staphylococcus aureus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of a bacterial multidrug ABC transporter., Dawson RJ, Locher KP, Nature. 2006 Sep 14;443(7108):180-5. Epub 2006 Aug 30. PMID:16943773
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