An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study

0189173 - UMCH-V 20033128 RIV US eng J - Journal Article
Skálová, Tereza - Hašek, Jindřich - Dohnálek, Jan - Petroková, Hana - Buchtelová, Eva - Dušková, Jarmila - Souček, Milan - Majer, Pavel - Kondrová, Taťána - Konvalinka, Jan
An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study.
Journal of Medicinal Chemistry. Roč. 46, č. 9 (2003), s. 1636-1644. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA AV ČR IAA4050811; GA AV ČR KJB4050312; GA ČR GV203/98/K023; GA ČR GA204/00/P091; GA ČR GA203/00/D117; GA MZd NI6339
Institutional research plan: CEZ:AV0Z4050913; CEZ:AV0Z4055905
Keywords : mutant HIV-1 protease * ethylenamine inhibitor * structure
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 4.820, year: 2003

An X-ray structure (resolution 2.2 A) of mutant HIV-1 protease (A71V, V82T, 184V) complexed with newly developed peptidomimetic inhibitor with ethyleneamine isostere Boc-Phe-.PSI.[CH2CH2NH]/Phe/Glu/Phe/NH2, denoted as OE, is described and compared with the complex of wild type HIV/1 protease with the same inhibitor (resolution 2.5 A). In the mutant protease weaker van der Waals interactions of the mutated residues Val 84 and Val 184 with OE were found. This lack of interaction energy is compensated by a new aromatic hydrogen bond between phenyl ring of the inhibitor in position P1 and the mutated residue Thr 182.
Permanent Link: http://hdl.handle.net/11104/0085014