4f4c: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4f4c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F4C FirstGlance]. <br>
<table><tr><td colspan='2'>[[4f4c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F4C FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0SA:UNDECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-1-THIO-BETA-D-GLUCOPYRANOSIDE'>0SA</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0SA:UNDECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-1-THIO-BETA-D-GLUCOPYRANOSIDE'>0SA</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4f4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f4c OCA], [https://pdbe.org/4f4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f4c RCSB], [https://www.ebi.ac.uk/pdbsum/4f4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f4c ProSAT]</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=4f4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f4c OCA], [https://pdbe.org/4f4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f4c RCSB], [https://www.ebi.ac.uk/pdbsum/4f4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f4c ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PGP1_CAEEL PGP1_CAEEL] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
[https://www.uniprot.org/uniprot/PGP1_CAEEL PGP1_CAEEL] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
P-glycoprotein (P-gp) is an ATP-binding cassette transporter that confers multidrug resistance in cancer cells. It also affects the absorption, distribution and clearance of cancer-unrelated drugs and xenobiotics. For these reasons, the structure and function of P-gp have been studied extensively for decades. Here we present biochemical characterization of P-gp from Caenorhabditis elegans and its crystal structure at a resolution of 3.4 angstroms. We find that the apparent affinities of P-gp for anticancer drugs actinomycin D and paclitaxel are approximately 4,000 and 100 times higher, respectively, in the membrane bilayer than in detergent. This affinity enhancement highlights the importance of membrane partitioning when a drug accesses the transporter in the membrane. Furthermore, the transporter in the crystal structure opens its drug pathway at the level of the membrane's inner leaflet. In the helices flanking the opening to the membrane, we observe extended loops that may mediate drug binding, function as hinges to gate the pathway or both. We also find that the interface between the transmembrane and nucleotide-binding domains, which couples ATP hydrolysis to transport, contains a ball-and-socket joint and salt bridges similar to the ATP-binding cassette importers, suggesting that ATP-binding cassette exporters and importers may use similar mechanisms to achieve alternating access for transport. Finally, a model of human P-gp derived from the structure of C. elegans P-gp not only is compatible with decades of biochemical analysis, but also helps to explain perplexing functional data regarding the Phe335Ala mutant. These results increase our understanding of the structure and function of this important molecule.
Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans.,Jin MS, Oldham ML, Zhang Q, Chen J Nature. 2012 Oct 25;490(7421):566-9. doi: 10.1038/nature11448. Epub 2012 Sep 23. PMID:23000902<ref>PMID:23000902</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4f4c" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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__TOC__
</StructureSection>
</StructureSection>

Revision as of 18:15, 14 March 2024

The Crystal Structure of the Multi-Drug TransporterThe Crystal Structure of the Multi-Drug Transporter

Structural highlights

4f4c is a 1 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.4Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PGP1_CAEEL Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.

4f4c, resolution 3.40Å

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