2opq: Difference between revisions

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-[[Image:2opq.png|left|200px]]
+==Crystal Structure of L100I Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.==
+<StructureSection load='2opq' size='340' side='right' caption='[[2opq]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2opq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1_m:b_hxb2r Hiv-1 m:b_hxb2r]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OPQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OPQ FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HBQ:ISOPROPYL+(2S)-2-ETHYL-7-FLUORO-3-OXO-3,4-DIHYDROQUINOXALINE-1(2H)-CARBOXYLATE'>HBQ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
+<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene></td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1 M:B_HXB2R])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2opq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2opq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2opq RCSB], [http://www.ebi.ac.uk/pdbsum/2opq PDBsum]</span></td></tr>
+<table>
+== 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/op/2opq_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 ==
+The selection of drug resistant viruses is a major problem in efforts to combat HIV and AIDS, hence, new compounds are required. We report crystal structures of wild-type and mutant HIV-1 RT with bound non-nucleoside (NNRTI) GW420867X, aimed at investigating the basis for its high potency and improved drug resistance profile compared to the first-generation drug nevirapine. GW420867X occupies a smaller volume than many NNRTIs, yet accesses key regions of the binding pocket. GW420867X has few contacts with Tyr188, hence, explaining the small effect of mutating this residue on inhibitor-binding potency. In a mutated NNRTI pocket, GW420867X either remains in a similar position compared to wild-type (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket (RT(Lys101Glu)). For RT(Leu100Ile), GW420867X does not shift position, in spite of forming different side-chain contacts. The small bulk of GW420867X allows adaptation to a mutated NNRTI binding site by repositioning or readjustment of side-chain contacts with only small reductions in binding affinity.
-{{STRUCTURE_2opq|  PDB=2opq  |  SCENE=  }}
+Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases.,Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK J Med Chem. 2007 May 17;50(10):2301-9. Epub 2007 Apr 19. PMID:17441703<ref>PMID:17441703</ref>
-===Crystal Structure of L100I Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_17441703}}
-==About this Structure==
-[[2opq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1_m:b_hxb2r Hiv-1 m:b_hxb2r]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OPQ OCA].
 ==See Also==
 *[[Reverse transcriptase|Reverse transcriptase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:017441703</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Hiv-1 m:b_hxb2r]]
 [[Category: RNA-directed DNA polymerase]]