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dc.contributor.authorDawson, Christopher D
dc.contributor.authorIrwin, Stephania M
dc.contributor.authorBackman, Lindsey RF
dc.contributor.authorLe, Chip
dc.contributor.authorWang, Jennifer X
dc.contributor.authorVennelakanti, Vyshnavi
dc.contributor.authorYang, Zhongyue
dc.contributor.authorKulik, Heather J
dc.contributor.authorDrennan, Catherine L
dc.contributor.authorBalskus, Emily P
dc.date.accessioned2021-10-27T20:24:02Z
dc.date.available2021-10-27T20:24:02Z
dc.date.issued2021
dc.identifier.urihttps://hdl.handle.net/1721.1/135563
dc.description.abstractDesulfonation 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.
dc.language.isoen
dc.publisherElsevier BV
dc.relation.isversionof10.1016/j.chembiol.2021.03.001
dc.rightsCreative Commons Attribution 4.0 International license
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceElsevier
dc.titleMolecular basis of C-S bond cleavage in the glycyl radical enzyme isethionate sulfite-lyase
dc.typeArticle
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineering
dc.contributor.departmentHoward Hughes Medical Institute
dc.relation.journalCell Chemical Biology
dc.eprint.versionFinal published version
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2021-06-14T12:27:33Z
dspace.orderedauthorsDawson, CD; Irwin, SM; Backman, LRF; Le, C; Wang, JX; Vennelakanti, V; Yang, Z; Kulik, HJ; Drennan, CL; Balskus, EP
dspace.date.submission2021-06-14T12:27:35Z
mit.journal.volume28
mit.journal.issue9
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Needed


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