Molecular basis of C-S bond cleavage in the glycyl radical enzyme isethionate sulfite-lyase.

ABSTRACT: Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces the disease-associated metabolite hydrogen sulfide. Here, we present a 2.7 Å resolution X-ray structure of wild-type IslA from Bilophila wadsworthia with isethionate bound. In comparison with other GREs, alternate positioning of the active site β strands allows for distinct residue positions to contribute to substrate binding. These structural differences, combined with sequence variations, create a highly tailored active site for the binding of the negatively charged isethionate substrate. Through the kinetic analysis of 14 IslA variants and computational analyses, we probe the mechanism by which radical chemistry i

SUBMITTER: Dawson CD 

PROVIDER: S-EPMC8473560 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature