Dynamics of preferential substrate recognition in HIV-1 protease: redefining the substrate envelope.

ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) protease (PR) permits viral maturation by processing the gag and gag-pro-pol polyproteins. HIV-1 PR inhibitors (PIs) are used in combination antiviral therapy but the emergence of drug resistance has limited their efficacy. The rapid evolution of HIV-1 necessitates consideration of drug resistance in novel drug design. Drug-resistant HIV-1 PR variants no longer inhibited efficiently, continue to hydrolyze the natural viral substrates. Though highly diverse in sequence, the HIV-1 PR substrates bind in a conserved three-dimensional shape we termed the substrate envelope. Earlier, we showed that resistance mutations arise where PIs protrude beyond the substrate envelope, because these regions are crucial for drug binding but not for substrate recogn

SUBMITTER: Ozen A 

PROVIDER: S-EPMC3139114 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature