Substrate envelope and drug resistance: crystal structure of RO1 in complex with wild-type human immunodeficiency virus type 1 protease.
In our previous crystallographic studies of human immunodeficiency virus type 1 (HIV-1) protease-substrate complexes, we described a conserved "envelope" that appears to be important for substrate recognition and the selection of drug-resistant mutations. In this study, the complex of HIV-1 protease with the inhibitor RO1 was determined and comparison with the substrate envelope provides a rationale for mutational patterns.
Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 01605, USA.
Moses
M
Prabu-Jeyabalan
Nancy M
NM
King
Ellen A
EA
Nalivaika
Gabrielle
G
Heilek-Snyder
Nick
N
Cammack
Celia A
CA
Schiffer
D003461:Crystallography; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D024882:Drug Resistance, Viral; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding
D004151:Dipeptides; D017320:HIV Protease Inhibitors; C510780:RO1 compound; D016333:HIV Protease