4dqe: Difference between revisions
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==Crystal Structure of (G16C/L38C) HIV-1 Protease in Complex with DRV== | ==Crystal Structure of (G16C/L38C) HIV-1 Protease in Complex with DRV== | ||
<StructureSection load='4dqe' size='340' side='right' caption='[[4dqe]], [[Resolution|resolution]] 1.30Å' scene=''> | <StructureSection load='4dqe' size='340' side='right' caption='[[4dqe]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dqe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4dqe]] 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=4DQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DQE 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></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></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dqb|4dqb]], [[4dqc|4dqc]], [[4dqf|4dqf]], [[4dqg|4dqg]], [[4dqh|4dqh]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dqb|4dqb]], [[4dqc|4dqc]], [[4dqf|4dqf]], [[4dqg|4dqg]], [[4dqh|4dqh]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-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">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4dqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dqe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dqe RCSB], [http://www.ebi.ac.uk/pdbsum/4dqe 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=4dqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dqe OCA], [http://pdbe.org/4dqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dqe RCSB], [http://www.ebi.ac.uk/pdbsum/4dqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dqe 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 4dqe" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Mittal, S]] | [[Category: Mittal, S]] | ||
[[Category: Schiffer, C A]] | [[Category: Schiffer, C A]] | ||
Revision as of 05:41, 11 December 2016
Crystal Structure of (G16C/L38C) HIV-1 Protease in Complex with DRVCrystal Structure of (G16C/L38C) HIV-1 Protease in Complex with DRV
Structural highlights
Publication Abstract from PubMedHuman immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity. Hydrophobic Core Flexibility Modulates Enzyme Activity in HIV-1 Protease.,Mittal S, Cai Y, Nalam MN, Bolon DN, Schiffer CA J Am Chem Soc. 2012 Mar 7;134(9):4163-8. Epub 2012 Feb 28. PMID:22295904[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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