View source for 3dok


==Crystal structure of K103N mutant HIV-1 reverse transcriptase in complex with GW678248.==
<StructureSection load='3dok' size='340' side='right'caption='[[3dok]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3dok]] is a 2 chain structure with sequence from [https://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=3DOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOK 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=GWJ:2-{4-CHLORO-2-[(3-CHLORO-5-CYANOPHENYL)CARBONYL]PHENOXY}-N-(2-METHYL-4-SULFAMOYLPHENYL)ACETAMIDE'>GWJ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3dok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dok OCA], [https://pdbe.org/3dok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dok RCSB], [https://www.ebi.ac.uk/pdbsum/3dok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dok ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A7YKL0_9HIV1 A7YKL0_9HIV1] 
== 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/do/3dok_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/main_output.php?pdb_ID=3dok ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Owing to the emergence of resistant virus, next generation non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) with improved drug resistance profiles have been developed to treat HIV infection. Crystal structures of HIV-1 RT complexed with benzophenones optimized for inhibition of HIV mutants that were resistant to the prototype benzophenone GF128590 indicate factors contributing to the resilience of later compounds in the series (GW4511, GW678248). Meta-substituents on the benzophenone A-ring had the designed effect of inducing better contacts with the conserved W229 while reducing aromatic stacking interactions with the highly mutable Y181 side chain, which unexpectedly adopted a "down" position. Up to four main-chain hydrogen bonds to the inhibitor also appear significant in contributing to resilience. Structures of mutant RTs (K103N, V106A/Y181C) with benzophenones showed only small rearrangements of the NNRTIs relative to wild-type. Hence, adaptation to a mutated NNRTI pocket by inhibitor rearrangement appears less significant for benzophenones than other next-generation NNRTIs.

Structural basis for the improved drug resistance profile of new generation benzophenone non-nucleoside HIV-1 reverse transcriptase inhibitors.,Ren J, Chamberlain PP, Stamp A, Short SA, Weaver KL, Romines KR, Hazen R, Freeman A, Ferris RG, Andrews CW, Boone L, Chan JH, Stammers DK J Med Chem. 2008 Aug 28;51(16):5000-8. Epub 2008 Jul 30. PMID:18665583<ref>PMID:18665583</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3dok" style="background-color:#fffaf0;"></div>

==See Also==
*[[Reverse transcriptase 3D structures|Reverse transcriptase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: HIV-1 M:B_HXB2R]]
[[Category: Large Structures]]
[[Category: Chamberlain PP]]
[[Category: Ren J]]
[[Category: Stammers DK]]