Entropy drives selective fluorine recognition in the fluoroacetyl-CoA thioesterase from Streptomyces cattleya.

ABSTRACT: Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. As such, there is strong interest in developing a deeper understanding of how fluorine affects the interaction of these ligands with their targets. Given the small number of fluorinated metabolites identified to date, insights into fluorine recognition have been provided almost entirely by synthetic systems. The fluoroacetyl-CoA thioesterase (FlK) from Streptomyces cattleya thus provides a unique opportunity to study an enzyme-ligand pair that has been evolutionarily optimized for a surprisingly high 10⁶ selectivity for a single fluorine substituent. In these studies, we synthesize a series of analogs of fluoroacetyl-CoA and acetyl-CoA to generate non

SUBMITTER: Weeks AM 

PROVIDER: S-EPMC5877923 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature