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| | ==P-glycoprotein cocrystallised with QZ-Leu== | | ==P-glycoprotein cocrystallised with QZ-Leu== |
| - | <StructureSection load='4q9k' size='340' side='right' caption='[[4q9k]], [[Resolution|resolution]] 3.80Å' scene=''> | + | <StructureSection load='4q9k' size='340' side='right'caption='[[4q9k]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4q9k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q9K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4q9k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9K FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=30F:(2Z)-2-AMINO-3-SELANYLPROP-2-ENOIC+ACID'>30F</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]] 3.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4q9h|4q9h]], [[4q9i|4q9i]], [[4q9j|4q9j]], [[4q9l|4q9l]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30F:(2Z)-2-AMINO-3-SELANYLPROP-2-ENOIC+ACID'>30F</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Xenobiotic-transporting_ATPase Xenobiotic-transporting ATPase], with EC number [http://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=4q9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9k OCA], [https://pdbe.org/4q9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9k RCSB], [https://www.ebi.ac.uk/pdbsum/4q9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9k 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=4q9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9k RCSB], [http://www.ebi.ac.uk/pdbsum/4q9k PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4q9k" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Xenobiotic-transporting ATPase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chang, G]] | + | [[Category: Mus musculus]] |
| - | [[Category: McGrath, A P]] | + | [[Category: Chang G]] |
| - | [[Category: Szewczyk, P]] | + | [[Category: McGrath AP]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | [[Category: Szewczyk P]] |
| - | [[Category: Membrane protein]]
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| - | [[Category: Transporter]]
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| Structural highlights
Function
MDR1A_MOUSE Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.[1]
Publication Abstract from PubMed
P-glycoprotein (P-gp) is a transporter of great clinical and pharmacological significance. Several structural studies of P-gp and its homologs have provided insights into its transport cycle, but questions remain regarding how P-gp recognizes diverse substrates and how substrate binding is coupled to ATP hydrolysis. Here, four new P-gp co-crystal structures with a series of rationally designed ligands are presented. It is observed that the binding of certain ligands, including an ATP-hydrolysis stimulator, produces a large conformational change in the fourth transmembrane helix, which is positioned to potentially transmit a signal to the nucleotide-binding domains. A new ligand-binding site on the surface of P-gp facing the inner leaflet of the membrane is also described, providing vital insights regarding the entry mechanism of hydrophobic drugs and lipids into P-gp. These results represent significant advances in the understanding of how P-gp and related transporters bind and export a plethora of metabolites, antibiotics and clinically approved and pipeline drugs.
Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein.,Szewczyk P, Tao H, McGrath AP, Villaluz M, Rees SD, Lee SC, Doshi R, Urbatsch IL, Zhang Q, Chang G Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):732-41. doi:, 10.1107/S1399004715000978. Epub 2015 Feb 26. PMID:25760620[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009 Mar 27;323(5922):1718-22. PMID:19325113 doi:323/5922/1718
- ↑ Szewczyk P, Tao H, McGrath AP, Villaluz M, Rees SD, Lee SC, Doshi R, Urbatsch IL, Zhang Q, Chang G. Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein. Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):732-41. doi:, 10.1107/S1399004715000978. Epub 2015 Feb 26. PMID:25760620 doi:http://dx.doi.org/10.1107/S1399004715000978
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