NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

ABSTRACT:

Background

The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation) in the absence of inhibitor and lining the substrate binding site (closed conformation) in the presence of an inhibitor.

Methods

In this work, nuclear magnetic resonance (NMR) spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution.

Findings

In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of

SUBMITTER: Su XC 

PROVIDER: S-EPMC2780355 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature