Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease.

ABSTRACT: HIV-1 protease recognizes and cleaves more than 12 different substrates leading to viral maturation. While these substrates share no conserved motif, they are specifically selected for and cleaved by protease during viral life cycle. Drug resistant mutations evolve within the protease that compromise inhibitor binding but allow the continued recognition of all these substrates. While the substrate envelope defines a general shape for substrate recognition, successfully predicting the determinants of substrate binding specificity would provide additional insights into the mechanism of altered molecular recognition in resistant proteases. We designed a variant of HIV protease with altered specificity using positive computational design methods and validated the design using X-ray crystallogr

SUBMITTER: Alvizo O 

PROVIDER: S-EPMC3403440 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature