The folding free-energy surface of HIV-1 protease: insights into the thermodynamic basis for resistance to inhibitors.

ABSTRACT: Spontaneous mutations at numerous sites distant from the active site of human immunodeficiency virus type 1 protease enable resistance to inhibitors while retaining enzymatic activity. As a benchmark for probing the effects of these mutations on the conformational adaptability of this dimeric beta-barrel protein, the folding free-energy surface of a pseudo-wild-type variant, HIV-PR(*), was determined by a combination of equilibrium and kinetic experiments on the urea-induced unfolding/refolding reactions. The equilibrium unfolding reaction was well described by a two-state model involving only the native dimeric form and the unfolded monomer. The global analysis of the kinetic folding mechanism reveals the presence of a fully folded monomeric intermediate that associates to form the native

SUBMITTER: Noel AF 

PROVIDER: S-EPMC2756696 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature