HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16970402
DOI
10.1021/jm0605583
Knihovny.cz E-resources
- MeSH
- Ethanolamines chemistry MeSH
- HIV Protease chemistry genetics MeSH
- HIV Protease Inhibitors chemistry MeSH
- Crystallography, X-Ray MeSH
- Ligands MeSH
- Models, Molecular * MeSH
- Molecular Structure MeSH
- Mutation MeSH
- Oligopeptides chemistry MeSH
- Binding Sites MeSH
- Hydrogen Bonding MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ethanolamines MeSH
- HIV Protease MeSH
- HIV Protease Inhibitors MeSH
- Ligands MeSH
- Oligopeptides MeSH
Two new X-ray structures of an HIV-1 protease mutant (A71V, V82T, I84V) in complex with inhibitors SE and SQ, pseudotetrapeptide inhibitors with an acyclic S-hydroxyethylamine isostere, were determined. Comparison of eight structures exploring the binding of four similar inhibitors--SE, SQ (S-hydroxyethylamine isostere), OE (ethyleneamine), and QF34 (hydroxyethylene)--to wild-type and A71V/V82T/I84V HIV-1 protease elucidates the principles of altered interaction with changing conditions. The A71V mutation, which is distant from the active site, causes changes in the structure of the enzyme detectable by the means of X-ray structure analysis, and a route of propagation of the effect toward the active site is proposed.
References provided by Crossref.org
PDB
1ZJ7, 1ZLF
