A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation and Subsite-Pocket Interactions Analyzed at Atomic Resolution

0191691 - UMG-J 20033207 RIV CZ eng K - Conference Paper (Czech conference)
Brynda, Jiří - Řezáčová, Pavlína - Fábry, Milan - Hořejší, Magdalena - Štouračová, Renata - Sedláček, Juraj - Souček, M. - Hradílek, M. - Lepšík, M. - Konvalinka, J.
A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation and Subsite-Pocket Interactions Analyzed at Atomic Resolution.
2003. In: Materials Structure in Chemistry, Biology, Physics and Technology. Czech and Slovak Crystallographic Association, s. 62. ISSN 1211-5894.
[Meeting of the Czech and Slovak structural biologists /3./. Nové hrady (CZ), 11.03.2004-13.03.2004]
R&D Projects: GA MŠMT OE67/1
Institutional research plan: CEZ:AV0Z5052915
Keywords : inhibitor * HIV protease * atomic resolution
Subject RIV: CE - Biochemistry

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.
Permanent Link: http://hdl.handle.net/11104/0087428