Název:
A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation and Subsite-Pocket Interactions Analyzed at Atomic Resolution
Autoři:
Brynda, Jiří ; Řezáčová, Pavlína ; Fábry, Milan ; Hořejší, Magdalena ; Štouračová, Renata ; Sedláček, Juraj ; Souček, M. ; Hradílek, M. ; Lepšík, M. ; Konvalinka, J. Typ dokumentu: Příspěvky z konference Konference/Akce: Meeting of the Czech and Slovak structural biologists /3./, Nové hrady (CZ), 2004-03-11 / 2004-03-13
Rok:
2003
Jazyk:
eng
Abstrakt: The x-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH2 has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibiot shows subnanomolar Ki values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance developoment. The structure displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. The high resolution permits to assess the donor/acceptor realtions of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. Structural mechanism for the unimpaired ihnibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses.
Klíčová slova:
atomic resolution; HIV protease; inhibitor Číslo projektu: CEZ:AV0Z5052915 (CEP), OE67/1 (CEP) Poskytovatel projektu: GA MŠk Zdrojový dokument: Materials Structure in Chemistry, Biology, Physics and Technology, ISSN 1211-5894
Instituce: Ústav molekulární genetiky AV ČR
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Informace o dostupnosti dokumentu:
Dokument je dostupný v příslušném ústavu Akademie věd ČR. Původní záznam: http://hdl.handle.net/11104/0087428