Electrostatic analysis of the hepatitis C virus NS3 helicase reveals both active and allosteric site locations.

ABSTRACT: Multi-conformation continuum electrostatics (MCCE) was used to analyze various structures of the NS3 RNA helicase from the hepatitis C virus in order to determine the ionization state of amino acid side chains and their pK(a)s. In MCCE analyses of HCV helicase structures that lacked ligands, several active site residues were identified to have perturbed pK(a)s in both the nucleic acid binding site and in the distant ATP-binding site, which regulates helicase movement. In all HCV helicase structures, Glu493 was unusually basic and His369 was abnormally acidic. Both these residues are part of the HCV helicase nucleic acid binding site, and their roles were analyzed by examining the pH profiles of site-directed mutants. Data support the accuracy of MCCE predicted pK(a) values, and reveal that

SUBMITTER: Frick DN 

PROVIDER: S-EPMC524300 | biostudies-literature | 2004

REPOSITORIES: biostudies-literature