View source for 2fle


==Structural analysis of asymmetric inhibitor bound to the HIV-1 Protease V82A mutant==
<StructureSection load='2fle' size='340' side='right' caption='[[2fle]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2fle]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AI:(2S,2S)-N,N-[(2S,3S,4S,5S)-1-CYCLOHEXYL-3,4-DIHYDROXY-6-PHENYLHEXANE-2,5-DIYL]BIS[3-METHYL-2-({[METHYL(PYRIDIN-2-YLMETHYL)AMINO]CARBONYL}AMINO)BUTANAMIDE]'>AI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=2fle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fle OCA], [http://pdbe.org/2fle PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fle RCSB], [http://www.ebi.ac.uk/pdbsum/2fle PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fle ProSAT]</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/fl/2fle_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=2fle ConSurf].
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== Publication Abstract from PubMed ==
In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. The binding affinity results indicate that these compounds have an improved response to the appearance of the V82A mutation than the parent compound. The X-ray structure of one of these compounds with the V82A HIV-1 PR variant provides the structural rationale for the better resistance profile of these compounds. Moreover, scrutiny of the X-ray structure suggests that the ring of the Cha side chain might be in a boat rather than in the chair conformation, a result supported by molecular dynamics simulations.

Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation.,Clemente JC, Robbins A, Grana P, Paleo MR, Correa JF, Villaverde MC, Sardina FJ, Govindasamy L, Agbandje-McKenna M, McKenna R, Dunn BM, Sussman F J Med Chem. 2008 Feb 28;51(4):852-60. Epub 2008 Jan 24. PMID:18215016<ref>PMID:18215016</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2fle" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clemente, J C]]
[[Category: Dunn, B M]]
[[Category: Robbins, A]]
[[Category: Sussman, F]]
[[Category: Hiv-1 protease]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Induced fit]]
[[Category: Inhibitor]]
[[Category: Resistance]]