Activation of the West Nile virus NS3 protease: molecular dynamics evidence for a conformational selection mechanism.

ABSTRACT: The flaviviral nonstructural 3 protease (NS3pro) is essential for virus replication and is therefore a pharmaceutically relevant target to fight Dengue and West Nile virus (WNV). NS3pro is a chymotrypsin-like serine protease which requires a polypeptide cofactor (NS2B) for activation. Recent X-ray crystallography studies have led to the suggestion that the substrate binds to the two-component NS2B-NS3pro enzyme by an induced-fit mechanism. Here, multiple explicit water molecular dynamics simulations of the WNV NS2B-NS3pro enzyme show that the active conformation of the NS2B cofactor (in which its beta-loop is part of the substrate binding site) is stable over a 50-ns time scale even in the absence of the inhibitor. The partial and reversible opening of the NSB2 beta-loop and its correlated

SUBMITTER: Ekonomiuk D 

PROVIDER: S-EPMC2771302 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature