View source for 2idw


==Crystal structure analysis of HIV-1 protease mutant V82A with a potent non-peptide inhibitor (UIC-94017)==
<StructureSection load='2idw' size='340' side='right'caption='[[2idw]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2idw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1s65 1s65]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IDW 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]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2idw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2idw OCA], [https://pdbe.org/2idw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2idw RCSB], [https://www.ebi.ac.uk/pdbsum/2idw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2idw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7SSI0_9HIV1 Q7SSI0_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/id/2idw_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=2idw ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
The compound UIC-94017 (TMC-114) is a second-generation HIV protease inhibitor with improved pharmacokinetics that is chemically related to the clinical inhibitor amprenavir. UIC-94017 is a broad-spectrum potent inhibitor active against HIV-1 clinical isolates with minimal cytotoxicity. We have determined the high-resolution crystal structures of UIC-94017 in complexes with wild-type HIV-1 protease (PR) and mutant proteases PR(V82A) and PR(I84V) that are common in drug-resistant HIV. The structures were refined at resolutions of 1.10-1.53A. The crystal structures of PR and PR(I84V) with UIC-94017 ternary complexes show that the inhibitor binds to the protease in two overlapping positions, while the PR(V82A) complex had one ordered inhibitor. In all three structures, UIC-94017 forms hydrogen bonds with the conserved main-chain atoms of Asp29 and Asp30 of the protease. These interactions are proposed to be critical for the potency of this compound against HIV isolates that are resistant to multiple protease inhibitors. Other small differences were observed in the interactions of the mutants with UIC-94017 as compared to PR. PR(V82A) showed differences in the position of the main-chain atoms of residue 82 compared to PR structure that better accommodated the inhibitor. Finally, the 1.10A resolution structure of PR(V82A) with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism.

High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains.,Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT J Mol Biol. 2004 Apr 23;338(2):341-52. PMID:15066436<ref>PMID:15066436</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 2idw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Boross PI]]
[[Category: Gaddis L]]
[[Category: Ghosh AK]]
[[Category: Harrison RW]]
[[Category: Hussain AK]]
[[Category: Leshchenko S]]
[[Category: Louis JM]]
[[Category: Manna D]]
[[Category: Tie Y]]
[[Category: Wang YF]]
[[Category: Weber IT]]