Modeling functional changes to Escherichia coli thymidylate synthase upon single residue replacements: a structure-based approach.

ABSTRACT: Escherichia coli thymidylate synthase (TS) is an enzyme that is indispensable to DNA synthesis and cell division, as it provides the only de novo source of dTMP by catalyzing the reductive methylation of dUMP, thus making it a key target for chemotherapeutic agents. High resolution X-ray crystallographic structures are available for TS and, owing to its relatively small size, successful experimental mutagenesis studies have been conducted on the enzyme. In this study, an in silico mutagenesis technique is used to investigate the effects of single amino acid substitutions in TS on enzymatic activity, one that employs the TS protein structure as well as a knowledge-based, four-body statistical potential. For every single residue TS variant, this approach yields both a global structural pertu

SUBMITTER: Masso M 

PROVIDER: S-EPMC4304848 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature