2hs1

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[[Image:2hs1.png|left|200px]]
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==Ultra-high resolution X-ray crystal structure of HIV-1 protease V32I mutant with TMC114 (darunavir) inhibitor==
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<StructureSection load='2hs1' size='340' side='right' caption='[[2hs1]], [[Resolution|resolution]] 0.84&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hs1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HS1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HS1 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
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<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=2hs1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hs1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hs1 RCSB], [http://www.ebi.ac.uk/pdbsum/2hs1 PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hs/2hs1_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 protease (PR) for treatment of drug resistant HIV/AIDS. We report the ultra-high 0.84 A resolution crystal structure of the TMC114 complex with PR containing the drug-resistant mutation V32I (PR(V32I)), and the 1.22 A resolution structure of a complex with PR(M46L). These structures show TMC114 bound at two distinct sites, one in the active-site cavity and the second on the surface of one of the flexible flaps in the PR dimer. Remarkably, TMC114 binds at these two sites simultaneously in two diastereomers related by inversion of the sulfonamide nitrogen. Moreover, the flap site is shaped to accommodate the diastereomer with the S-enantiomeric nitrogen rather than the one with the R-enantiomeric nitrogen. The existence of the second binding site and two diastereomers suggest a mechanism for the high effectiveness of TMC114 on drug-resistant HIV and the potential design of new inhibitors.
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{{STRUCTURE_2hs1| PDB=2hs1 | SCENE= }}
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Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114.,Kovalevsky AY, Liu F, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT J Mol Biol. 2006 Oct 13;363(1):161-73. Epub 2006 Aug 4. PMID:16962136<ref>PMID:16962136</ref>
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===Ultra-high resolution X-ray crystal structure of HIV-1 protease V32I mutant with TMC114 (darunavir) inhibitor===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_16962136}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[2hs1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HS1 OCA].
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:016962136</ref><references group="xtra"/>
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[[Category: HIV-1 retropepsin]]
[[Category: HIV-1 retropepsin]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]

Revision as of 08:00, 30 September 2014

Ultra-high resolution X-ray crystal structure of HIV-1 protease V32I mutant with TMC114 (darunavir) inhibitor

2hs1, resolution 0.84Å

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