Efficient methylation of C2 in l-tryptophan by the cobalamin-dependent radical S-adenosylmethionine methylase TsrM requires an unmodified N1 amine.

ABSTRACT: TsrM catalyzes the methylation of C2 in l-tryptophan (Trp). This reaction is the first step in the biosynthesis of the quinaldic acid moiety of the thiopeptide antibiotic thiostrepton, which exhibits potent activity against Gram-positive pathogens. TsrM is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes, but it does not catalyze the formation of 5'-deoxyadenosin-5'-yl or any other SAM-derived radical. In addition to a [4Fe-4S] cluster, TsrM contains a cobalamin cofactor that serves as an intermediate methyl carrier in its reaction. However, how this cofactor donates a methyl moiety to the Trp substrate is unknown. Here, we showed that the unmodified N1 position of Trp is important for turnover and that 1-thia-Trp and 1-oxa-Trp serve as competitive inhibitor

SUBMITTER: Blaszczyk AJ 

PROVIDER: S-EPMC5602403 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature