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| | ==Corrected Structure of Mouse P-glycoprotein== | | ==Corrected Structure of Mouse P-glycoprotein== |
| - | <StructureSection load='4m1m' size='340' side='right' caption='[[4m1m]], [[Resolution|resolution]] 3.80Å' scene=''> | + | <StructureSection load='4m1m' size='340' side='right'caption='[[4m1m]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M1M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m1m]] 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=4M1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m2s|4m2s]], [[4m2t|4m2t]], [[3g5u|3g5u]], [[3g60|3g60]], [[3g61|3g61]]</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=4m1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1m OCA], [https://pdbe.org/4m1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1m RCSB], [https://www.ebi.ac.uk/pdbsum/4m1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1m ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Abcb1a, Abcb4, Mdr1a, Mdr3, Pgy-3, Pgy3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1m OCA], [http://pdbe.org/4m1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m1m RCSB], [http://www.ebi.ac.uk/pdbsum/4m1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1m ProSAT]</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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Xenobiotic-transporting ATPase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Aller, S G]] | + | [[Category: Aller SG]] |
| - | [[Category: Jaimes, K F]] | + | [[Category: Jaimes KF]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Adenosine triphosphate]]
| + | |
| - | [[Category: Atp-binding cassette transporter]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mercurated cysteine]]
| + | |
| - | [[Category: Multidrug efflux]]
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| - | [[Category: Plasma membrane]]
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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
The recently determined C. elegans P-glycoprotein (Pgp) structure revealed significant deviations compared to the original mouse Pgp structure, which suggested possible misinterpretations in the latter model. To address this concern, we generated an experimental electron density map from single-wavelength anomalous dispersion phasing of an original mouse Pgp dataset to 3.8 A resolution. The map exhibited significantly more detail compared to the original MAD map and revealed several regions of the structure that required de novo model building. The improved drug-free structure was refined to 3.8 A resolution with a 9.4% and 8.1% decrease in Rwork and Rfree , respectively (Rwork =21.2%, Rfree =26.6%) and a significant improvement in protein geometry. The improved mouse Pgp model contains ~ 95% of residues in the favorable Ramachandran region compared to only 57% for the original model. The registry of six transmembrane helices was corrected, revealing amino acid residues involved in drug binding that were previously unrecognized. Registry shifts (rotations and translations) for TM4 and TM5 and the addition of three N-terminal residues were necessary, and were validated with new mercury labeling and anomalous fourier density. The corrected position of TM4, which forms the frame of a portal for drug entry, had backbone atoms shifted > 6 A from their original positions. The drug translocation pathway of mouse Pgp is 96% identical to human Pgp and is enriched in aromatic residues that likely play a collective role in allowing a high degree of polyspecificity in substrate recognition.
Refined structures of mouse P-Glycoprotein.,Li J, Jaimes KF, Aller SG Protein Sci. 2013 Oct 24. doi: 10.1002/pro.2387. PMID:24155053[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
- ↑ Li J, Jaimes KF, Aller SG. Refined structures of mouse P-Glycoprotein. Protein Sci. 2013 Oct 24. doi: 10.1002/pro.2387. PMID:24155053 doi:http://dx.doi.org/10.1002/pro.2387
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