3g60: Difference between revisions
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==Structure of P-glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding== | |||
<StructureSection load='3g60' size='340' side='right' caption='[[3g60]], [[Resolution|resolution]] 4.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3g60]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. The March 2010 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''P-glycoprotein'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2010_3 10.2210/rcsb_pdb/mom_2010_3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G60 FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JZ:(4R,11R,18R)-4,11,18-TRI(PROPAN-2-YL)-6,13,20-TRISELENA-3,10,17,22,23,24-HEXAAZATETRACYCLO[17.2.1.1~5,8~.1~12,15~]TETRACOSA-1(21),5(24),7,12(23),14,19(22)-HEXAENE-2,9,16-TRIONE'>0JZ</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3g5u|3g5u]], [[3g61|3g61]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Abcb1a, mCG_1178 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3g60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g60 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g60 RCSB], [http://www.ebi.ac.uk/pdbsum/3g60 PDBsum]</span></td></tr> | |||
</table> | |||
== 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> | [[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> | ||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g6/3g60_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding. | |||
Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding.,Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G Science. 2009 Mar 27;323(5922):1718-22. PMID:19325113<ref>PMID:19325113</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lk3 transgenic mice]] | [[Category: Lk3 transgenic mice]] | ||
[[Category: P-glycoprotein]] | [[Category: P-glycoprotein]] | ||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Aller, S G | [[Category: Aller, S G]] | ||
[[Category: Chang, G | [[Category: Chang, G]] | ||
[[Category: Chittaboina, S | [[Category: Chittaboina, S]] | ||
[[Category: Harrell, P M | [[Category: Harrell, P M]] | ||
[[Category: Trinh, Y T | [[Category: Trinh, Y T]] | ||
[[Category: Urbatsch, I L | [[Category: Urbatsch, I L]] | ||
[[Category: Ward, A | [[Category: Ward, A]] | ||
[[Category: Weng, Y | [[Category: Weng, Y]] | ||
[[Category: Yu, J | [[Category: Yu, J]] | ||
[[Category: Zhang, Q | [[Category: Zhang, Q]] | ||
[[Category: Zhuo, R | [[Category: Zhuo, R]] | ||
[[Category: Cyclic peptide]] | [[Category: Cyclic peptide]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
[[Category: Multidrug resistance]] | [[Category: Multidrug resistance]] | ||
[[Category: Pgp]] | [[Category: Pgp]] | ||
Revision as of 07:15, 25 December 2014
Structure of P-glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
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