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[[Image: | ==STRUCTURAL BASIS OF DRUG RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEASE: BACKBONE FLEXIBILITY AND SUBSITE REPACKING== | ||
<StructureSection load='1hvs' size='340' side='right' caption='[[1hvs]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1hvs]] 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=1HVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HVS FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A77:N-{1-BENZYL-(2R,3S)-2,3-DIHYDROXY-4-[3-METHYL-2-(3-METHYL-3-PYRIDIN-2-YLMETHYL-UREIDO)-BUTYRYLAMINO]-5-PHENYL-PENTYL}-3-METHYL-2-(3-METHYL-3-PYRIDIN-2-YLMETHYL-UREIDO)-BUTYRAMIDE'>A77</scene><br> | |||
<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=1hvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hvs RCSB], [http://www.ebi.ac.uk/pdbsum/1hvs PDBsum]</span></td></tr> | |||
<table> | |||
== 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/hv/1hvs_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A major problem in the development of antiviral therapies for AIDS has been the emergence of drug resistance. We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor. Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1' subsites. Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1' subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic. | |||
Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase.,Baldwin ET, Bhat TN, Liu B, Pattabiraman N, Erickson JW Nat Struct Biol. 1995 Mar;2(3):244-9. PMID:7773792<ref>PMID:7773792</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Baldwin, E T.]] | [[Category: Baldwin, E T.]] | ||
Revision as of 14:20, 28 September 2014
STRUCTURAL BASIS OF DRUG RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEASE: BACKBONE FLEXIBILITY AND SUBSITE REPACKINGSTRUCTURAL BASIS OF DRUG RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEASE: BACKBONE FLEXIBILITY AND SUBSITE REPACKING
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA major problem in the development of antiviral therapies for AIDS has been the emergence of drug resistance. We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor. Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1' subsites. Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1' subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic. Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase.,Baldwin ET, Bhat TN, Liu B, Pattabiraman N, Erickson JW Nat Struct Biol. 1995 Mar;2(3):244-9. PMID:7773792[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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