Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor.

ABSTRACT: Dimerization is indispensible for release of the human immunodeficiency virus protease (PR) from its precursor (Gag-Pol) and ensuing mature-like catalytic activity that is crucial for virus maturation. We show that a single-chain Fv fragment (scFv) of a previously reported monoclonal antibody (mAb1696), which recognizes the N-terminus of PR, dissociates a dimeric mature D25N PR mutant with an enhanced dimer dissociation constant (K(d)) in the sub-micromolar range to form predominantly a monomer-scFv complex at a 1:1 ratio, along with small (5-10%) amounts of a dimer-scFv complex. Enzyme kinetics indicate a mixed mechanism of inhibition of the wild-type PR, which exhibits a K(d)<10nM, with effects both on K(m) and k(cat) at an scFv-to-PR ratio of 10:1. ScFv binds to the N-terminal peptide P

SUBMITTER: Sayer JM 

PROVIDER: S-EPMC3418415 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature