0188952 - UMCH-V 20023367 RIV US eng J - Journal Article
Dohnálek, Jan - Hašek, Jindřich - Dušková, Jarmila - Petroková, Hana - Hradilek, Martin - Souček, Milan - Konvalinka, Jan - Brynda, Jiří - Sedláček, Juraj - Fábry, Milan
Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor.
Journal of Medicinal Chemistry. Roč. 45, č. 7 (2002), s. 1432-1438. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA AV ČR IAA4050811; GA ČR GA203/97/P031; GA ČR GV203/98/K023; GA ČR GA203/00/D117; GA ČR GA204/00/P091
Institutional research plan: CEZ:AV0Z4050913
Keywords : HIV-1 protease * hydroxyethylamine-containing inhibitor * aspartate
Subject RIV: CE - Biochemistry
Impact factor: 4.566, year: 2002

A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-.Psi.[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 Angstrom resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors.
Permanent Link: http://hdl.handle.net/11104/0084819