Structural basis of substrate recognition by a novel thermostable (S)-enantioselective ?-transaminase from Thermomicrobium roseum.

ABSTRACT: Transaminases catalyze the reversible transfer reaction of an amino group between a primary amine and an ?-keto acid, utilizing pyridoxal 5'-phosphate as a cofactor. ?-transaminases (?TAs) recognize an amino group linked to a non-? carbon of amine substrates. Recently, a novel (S)-enantioselective ?TA from Thermomicrobium roseum (Tr-?TA) was identified and its enzymatic activity reported. However, the detailed mechanism of (S)-enantioselective substrate recognition remained unclear. In this study, we determined the crystal structure of Tr-?TA at 1.8?Å resolution to elucidate the mechanism underlying Tr-?TA substrate (S)-enantioselectivity. A structural analysis of Tr-?TA along with molecular docking simulations revealed that two pockets at the active site tightly restrict the size and orientation of functional groups of substrate candidates. Based on the structural information and docking simulation results, we propose a comprehensive catalytic mechanism of Tr-?TA. The present study thus provides structural and functional insights into the (S)-enantioselectivity of Tr-?TA.

SUBMITTER: Kwon S 

PROVIDER: S-EPMC6502798 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature