4q9j: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==P-glycoprotein cocrystallised with QZ-Val== | |||
<StructureSection load='4q9j' size='340' side='right'caption='[[4q9j]], [[Resolution|resolution]] 3.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4q9j]] is a 4 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=4Q9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9J FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.6Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4q9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9j OCA], [https://pdbe.org/4q9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9j RCSB], [https://www.ebi.ac.uk/pdbsum/4q9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9j ProSAT]</span></td></tr> | |||
</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 == | |||
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<ref>PMID:25760620</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4q9j" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Chang G]] | |||
[[Category: McGrath AP]] | |||
[[Category: Szewczyk P]] | |||
