Preserved hydride transfer mechanism in evolutionarily divergent thymidylate synthases.

ABSTRACT: Thymidylate synthase (TSase) catalyzes a hydride transfer in the last step of the de novo biosynthesis of the DNA nucleotide thymine. We compared two isozymes, namely, TSase from Escherichia coli (ecTSase) and TSase from Bacillus subtilis (bsTSase) that represent a case of divergent evolution. Interestingly, a highly conserved histidine (H147 of ecTSase) was proposed to serve a critical role in catalysis, but in bsTSase it is naturally substituted by valine (Val). Yet, bsTSase is more active than ecTSase, and the intrinsic kinetic isotope effects (KIEs) of both are temperature-independent, suggesting a similarly well-organized transition state (TS) for the catalyzed hydride transfer. To examine the role of that histidine (His)

SUBMITTER: Abeysinghe T 

PROVIDER: S-EPMC5172458 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature