Substrate envelope and drug resistance: crystal structure of RO1 in complex with wild-type human immunodeficiency virus type 1 protease

Moses Prabu-Jeyabalan, University of Massachusetts Medical School
Nancy M. King, University of Massachusetts Medical School
Ellen A. Nalivaika, University of Massachusetts Medical School
Gabrielle Heilek-Snyder
Nick Cammack
Celia A. Schiffer, University of Massachusetts Medical School

Abstract

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.