1hvs
STRUCTURAL BASIS OF DRUG RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEASE: BACKBONE FLEXIBILITY AND SUBSITE REPACKING
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| , resolution 2.25Å | |||||||
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OverviewOverview
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.
About this StructureAbout this Structure
1HVS is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
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
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