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
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16970402
DOI
10.1021/jm0605583
Knihovny.cz E-zdroje
- MeSH
- ethanolaminy chemie MeSH
- HIV-proteasa chemie genetika MeSH
- inhibitory HIV-proteasy chemie MeSH
- krystalografie rentgenová MeSH
- ligandy MeSH
- molekulární modely * MeSH
- molekulární struktura MeSH
- mutace MeSH
- oligopeptidy chemie MeSH
- vazebná místa MeSH
- vodíková vazba MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ethanolaminy MeSH
- HIV-proteasa MeSH
- inhibitory HIV-proteasy MeSH
- ligandy MeSH
- oligopeptidy 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.
Citace poskytuje Crossref.org
PDB
1ZJ7, 1ZLF
