3s54: Difference between revisions
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==HIV-1 protease triple mutants V32I, I47V, V82I with antiviral drug darunavir in space group P21212== | ==HIV-1 protease triple mutants V32I, I47V, V82I with antiviral drug darunavir in space group P21212== | ||
<StructureSection load='3s54' size='340' side='right' caption='[[3s54]], [[Resolution|resolution]] 1.42Å' scene=''> | <StructureSection load='3s54' size='340' side='right' caption='[[3s54]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3s54]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3s54]] 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=3S54 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S54 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ien|2ien]], [[3ebz|3ebz]], [[3s43|3s43]], [[3s53|3s53]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ien|2ien]], [[3ebz|3ebz]], [[3s43|3s43]], [[3s53|3s53]]</td></tr> | ||
<tr id='gene'><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 | <tr id='gene'><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 9HIV1])</td></tr> | ||
<tr id='activity'><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> | <tr id='activity'><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> | ||
<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=3s54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s54 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s54 RCSB], [http://www.ebi.ac.uk/pdbsum/3s54 PDBsum]</span></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=3s54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s54 OCA], [http://pdbe.org/3s54 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s54 RCSB], [http://www.ebi.ac.uk/pdbsum/3s54 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s54 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3s54" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Tie, Y F]] | [[Category: Tie, Y F]] | ||
[[Category: Wang, Y F]] | [[Category: Wang, Y F]] | ||
Revision as of 22:23, 11 August 2016
Structural highlights
Publication Abstract from PubMedClinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR) than on HIV-1 protease (PR). We solved the crystal structure of PR with APV at 1.5 A resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR. PR(1M) more closely resembled PR than PR in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR(1M) with APV, DRV, and SQV were compared with available PR and PR complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR(1M) and PR, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR(1M). Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR (M) and PR relative to the strong hydrogen bonds observed in PR, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR(1M) partially replicates the specificity of PR and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2. Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors.,Tie Y, Wang YF, Boross PI, Chiu TY, Ghosh AK, Tozser J, Louis JM, Harrison RW, Weber IT Protein Sci. 2012 Mar;21(3):339-50. doi: 10.1002/pro.2019. Epub 2012 Jan 24. PMID:22238126[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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