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

Brynda, Jiří; Řezáčová, Pavlína; Fábry, Milan; Hořejší, Magdalena; Štouračová, Renata; Sedláček, Juraj; Souček, Milan; Hradilek, Martin; Lepšík, Martin; Konvalinka, Jan

Number of the records: 1

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

1.

SYSNO ASEP	0108979
Document Type	K - Proceedings Paper (Czech conf.)
R&D Document Type	Conference Paper
Title	A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation and Subsite-Pocket Interactions Analyzed at Atomic Resolution
Title	Vazba fenylnorstatinového inhibitoru na proteázu HIV-1: geometrie, protonace a interakce kapes podřadných míst analyzované při atomovém rozlišení
Author(s)	Brynda, Jiří (UMG-J)_RID Řezáčová, Pavlína (UMG-J)_RID Fábry, Milan (UMG-J)_RID Hořejší, Magdalena (UMG-J) Štouračová, Renata (UMG-J) Sedláček, Juraj (UMG-J)_RID Souček, Milan (UOCHB-X) Hradilek, Martin (UOCHB-X)_ORCID Lepšík, Martin (UOCHB-X)_{RID, ORCID} Konvalinka, Jan (UOCHB-X)_{RID, ORCID}
Issue data	2004
Source Title	Materials Structure in Chemistry, Biology, Physics and Technology. - : Czech and Slovak Crystallographic Association - ISSN 1211-5894 s. 62
Number of pages	1 s.
Action	Meeting of the Czech and Slovak structural biologists /3./
Event date	11.03.2004-13.03.2004
VEvent location	Nové hrady
Country	CZ - Czech Republic
Event type	EUR
Language	eng - English
Country	CZ - Czech Republic
Keywords	inhibitor ; HIV protease ; atomic resolution
Subject RIV	CE - Biochemistry
R&D Projects	OE67/1 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
CEZ	AV0Z5052915 - UMG-J
Annotation	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 development. The structure displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. The high resolution permints to assess the donor/acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. Structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2005

Number of the records: 1