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dc.contributor.authorBridwell-Rabb, Jennifer
dc.contributor.authorLi, Bin
dc.contributor.authorDrennan, Catherine L
dc.date.accessioned2022-12-07T18:43:44Z
dc.date.available2022-12-07T18:43:44Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/146791
dc.description.abstractThe members of the radical S-adenosylmethionine (SAM) enzyme superfamily are responsible for catalyzing a diverse set of reactions in a multitude of biosynthetic pathways. Many members of this superfamily accomplish their transformations using the catalytic power of a 5'-deoxyadenosyl radical (5'-dAdo•), but there are also enzymes within this superfamily that bind auxiliary cofactors and extend the catalytic repertoire of SAM. In particular, the cobalamin (Cbl)-dependent class synergistically uses Cbl to facilitate challenging methylation and radical rearrangement reactions. Despite identification of this class by Sofia et al. 20 years ago, the low sequence identity between members has led to difficulty in predicting function of uncharacterized members, pinpointing catalytic residues, and elucidating reaction mechanisms. Here, we capitalize on the three recent structures of Cbl-dependent radical SAM enzymes that use common cofactors to facilitate ring contraction as well as radical-based and non-radical-based methylation reactions. With these three structures as a framework, we describe how the Cbl-dependent radical SAM enzymes repurpose the traditional SAM- and Cbl-binding motifs to form an active site where both Cbl and SAM can participate in catalysis. In addition, we describe how, in some cases, the classic SAM- and Cbl-binding motifs support the diverse functionality of this enzyme class, and finally, we define new motifs that are characteristic of Cbl-dependent radical SAM enzymes.en_US
dc.language.isoen
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionof10.1021/ACSBIOMEDCHEMAU.1C00051en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceACSen_US
dc.titleCobalamin-Dependent Radical S -Adenosylmethionine Enzymes: Capitalizing on Old Motifs for New Functionsen_US
dc.typeArticleen_US
dc.identifier.citationBridwell-Rabb, Jennifer, Li, Bin and Drennan, Catherine L. 2022. "Cobalamin-Dependent Radical S -Adenosylmethionine Enzymes: Capitalizing on Old Motifs for New Functions." ACS Bio & Med Chem Au, 2 (3).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalACS Bio & Med Chem Auen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-12-07T18:34:24Z
dspace.orderedauthorsBridwell-Rabb, J; Li, B; Drennan, CLen_US
dspace.date.submission2022-12-07T18:34:28Z
mit.journal.volume2en_US
mit.journal.issue3en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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