Molecular recognition of fluorine impacts substrate selectivity in the fluoroacetyl-CoA thioesterase FlK.

ABSTRACT: The fluoroacetate-producing bacterium Streptomyces cattleya has evolved a fluoroacetyl-CoA thioesterase (FlK) that exhibits a remarkably high level of discrimination for its cognate substrate compared to the cellularly abundant analogue acetyl-CoA, which differs only by the absence of the fluorine substitution. A major determinant of FlK specificity derives from its ability to take advantage of the unique properties of fluorine to enhance the reaction rate, allowing fluorine discrimination under physiological conditions where both substrates are likely to be present at saturating concentrations. Using a combination of pH-rate profiles, pre-steady-state kinetic experiments, and Taft analysis of wild-type and mutant FlKs with a set of substrate analogues, we explore the role of fluorine in c

SUBMITTER: Weeks AM 

PROVIDER: S-EPMC3985765 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature