3u7s

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[[Image:3u7s.jpg|left|200px]]
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==HIV PR drug resistant patient's variant in complex with darunavir==
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<StructureSection load='3u7s' size='340' side='right' caption='[[3u7s]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3u7s]] is a 2 chain structure with sequence from [http://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=3ggt 3ggt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U7S 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=BME:BETA-MERCAPTOETHANOL'>BME</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ggu|1ggu]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([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=3u7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u7s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u7s RCSB], [http://www.ebi.ac.uk/pdbsum/3u7s PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Darunavir is the most recently approved human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) and is active against many HIV type 1 PR variants resistant to earlier-generation PIs. Darunavir shows a high genetic barrier to resistance development, and virus strains with lower sensitivity to darunavir have a higher number of PI resistance-associated mutations than viruses resistant to other PIs. In this work, we have enzymologically and structurally characterized a number of highly mutated clinically derived PRs with high levels of phenotypic resistance to darunavir. With 18 to 21 amino acid residue changes, the PR variants studied in this work are the most highly mutated HIV PR species ever studied by means of enzyme kinetics and X-ray crystallography. The recombinant proteins showed major defects in substrate binding, while the substrate turnover was less affected. Remarkably, the overall catalytic efficiency of the recombinant PRs (5% that of the wild-type enzyme) is still sufficient to support polyprotein processing and particle maturation in the corresponding viruses. The X-ray structures of drug-resistant PRs complexed with darunavir suggest that the impaired inhibitor binding could be explained by change in the PR-inhibitor hydrogen bond pattern in the P2' binding pocket due to a substantial shift of the aminophenyl moiety of the inhibitor. Recombinant virus phenotypic characterization, enzyme kinetics, and X-ray structural analysis thus help to explain darunavir resistance development in HIV-positive patients.
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Molecular characterization of clinical isolates of human immunodeficiency virus resistant to the protease inhibitor darunavir.,Saskova KG, Kozisek M, Rezacova P, Brynda J, Yashina T, Kagan RM, Konvalinka J J Virol. 2009 Sep;83(17):8810-8. Epub 2009 Jun 17. PMID:19535439<ref>PMID:19535439</ref>
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The line below this paragraph, containing "STRUCTURE_3u7s", creates the "Structure Box" on the page.
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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or leave the SCENE parameter empty for the default display.
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{{STRUCTURE_3u7s| PDB=3u7s | SCENE= }}
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===HIV PR drug resistant patient's variant in complex with darunavir===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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The line below this paragraph, {{ABSTRACT_PUBMED_19535439}}, adds the Publication Abstract to the page
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__TOC__
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(as it appears on PubMed at http://www.pubmed.gov), where 19535439 is the PubMed ID number.
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</StructureSection>
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{{ABSTRACT_PUBMED_19535439}}
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==About this Structure==
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[[3u7s]] is a 2 chain structure with sequence from [http://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=3ggt 3ggt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7S OCA].
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==Reference==
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<ref group="xtra">PMID:019535439</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 05:47, 5 June 2014

HIV PR drug resistant patient's variant in complex with darunavir

3u7s, resolution 2.05Å

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