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Molecular basis of C-S bond cleavage in the glycyl radical enzyme isethionate sulfite-lyase.
- Source :
-
Cell chemical biology [Cell Chem Biol] 2021 Sep 16; Vol. 28 (9), pp. 1333-1346.e7. Date of Electronic Publication: 2021 Mar 26. - Publication Year :
- 2021
-
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 is used for C-S bond cleavage. This work further elucidates the structural basis of chemistry within the GRE superfamily and will inform structure-based inhibitor design of IsIA and thus of microbial hydrogen sulfide production.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2451-9448
- Volume :
- 28
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 33773110
- Full Text :
- https://doi.org/10.1016/j.chembiol.2021.03.001