7otg
From Proteopedia
(Difference between revisions)
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==Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor== | ==Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor== | ||
| - | <StructureSection load='7otg' size='340' side='right'caption='[[7otg]]' scene=''> | + | <StructureSection load='7otg' size='340' side='right'caption='[[7otg]], [[Resolution|resolution]] 5.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OTG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7otg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OTG FirstGlance]. <br> |
| - | </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=7otg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7otg OCA], [https://pdbe.org/7otg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7otg RCSB], [https://www.ebi.ac.uk/pdbsum/7otg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7otg ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VX7:N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide'>VX7</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Xenobiotic-transporting_ATPase Xenobiotic-transporting ATPase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.44 3.6.3.44] </span></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=7otg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7otg OCA], [https://pdbe.org/7otg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7otg RCSB], [https://www.ebi.ac.uk/pdbsum/7otg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7otg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/MDR1A_MOUSE MDR1A_MOUSE]] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.<ref>PMID:19325113</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of the protein within the membrane is an intrinsic part of its mechanism of action, but this has made structural studies challenging. Here, we have studied different conformations of P-glycoprotein simultaneously in the presence of ivacaftor, a known competitive inhibitor. In order to conduct this, we used high contrast cryo-electron microscopy imaging with a Volta phase plate. We associate the presence of ivacaftor with the appearance of an additional density in one of the conformational states detected. The additional density is in the central aqueous cavity and is associated with a wider separation of the two halves of the transporter in the inward-facing state. Conformational changes to the nucleotide-binding domains are also observed and may help to explain the stimulation of ATPase activity that occurs when transported substrate is bound in many ATP binding cassette transporters. | ||
| + | |||
| + | Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor.,Barbieri A, Thonghin N, Shafi T, Prince SM, Collins RF, Ford RC Membranes (Basel). 2021 Nov 25;11(12). pii: membranes11120923. doi:, 10.3390/membranes11120923. PMID:34940424<ref>PMID:34940424</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7otg" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Barbieri A]] | + | [[Category: Xenobiotic-transporting ATPase]] |
| - | [[Category: Collins | + | [[Category: Barbieri, A]] |
| - | [[Category: Ford | + | [[Category: Collins, R F]] |
| - | [[Category: Prince | + | [[Category: Ford, R C]] |
| - | [[Category: Shafi T]] | + | [[Category: Prince, S M]] |
| - | [[Category: Thonghin N]] | + | [[Category: Shafi, T]] |
| + | [[Category: Thonghin, N]] | ||
| + | [[Category: Abc transporter]] | ||
| + | [[Category: Abcb1]] | ||
| + | [[Category: Cryo-em]] | ||
| + | [[Category: Ivacaftor]] | ||
| + | [[Category: Mdr1]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Multidrug resistance]] | ||
Revision as of 10:45, 5 January 2022
Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor
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