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dc.contributor.authorDowling, Daniel P.
dc.contributor.authorVey, Jessica L.
dc.contributor.authorCroft, Anna K.
dc.contributor.authorDrennan, Catherine L.
dc.date.accessioned2017-05-26T19:00:49Z
dc.date.available2017-05-26T19:00:49Z
dc.date.issued2012-11
dc.date.submitted2012-04
dc.identifier.issn15709639
dc.identifier.urihttp://hdl.handle.net/1721.1/109390
dc.description.abstractAdoMet radical enzymes are involved in processes such as cofactor biosynthesis, anaerobic metabolism, and natural product biosynthesis. These enzymes utilize the reductive cleavage of S-adenosylmethionine (AdoMet) to afford l-methionine and a transient 5′-deoxyadenosyl radical, which subsequently generates a substrate radical species. By harnessing radical reactivity, the AdoMet radical enzyme superfamily is responsible for an incredible diversity of chemical transformations. Structural analysis reveals that family members adopt a full or partial Triose-phosphate Isomerase Mutase (TIM) barrel protein fold, containing core motifs responsible for binding a catalytic [4Fe–4S] cluster and AdoMet. Here we evaluate over twenty structures of AdoMet radical enzymes and classify them into two categories: ‘traditional’ and ‘ThiC-like’ (named for the structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase (ThiC)). In light of new structural data, we reexamine the ‘traditional’ structural motifs responsible for binding the [4Fe–4S] cluster and AdoMet, and compare and contrast these motifs with the ThiC case. We also review how structural data combine with biochemical, spectroscopic, and computational data to help us understand key features of this enzyme superfamily, such as the energetics, the triggering, and the molecular mechanisms of AdoMet reductive cleavage. This article is part of a Special Issue entitled: Radical SAM Enzymes and Radical Enzymology.en_US
dc.description.sponsorshipWellcome Trust (London, England) (091162/Z/10/Z)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (NSF Grant MCB-0543833)en_US
dc.description.sponsorshipHoward Hughes Medical Institute (Investigator)en_US
dc.language.isoen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.bbapap.2012.04.006en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleStructural diversity in the AdoMet radical enzyme superfamilyen_US
dc.typeArticleen_US
dc.identifier.citationDowling, Daniel P., Jessica L. Vey, Anna K. Croft, and Catherine L. Drennan. "Structural diversity in the AdoMet radical enzyme superfamily." Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Volume 1824, Issue 11, (November 2012), pp. 1178-1195.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorDowling, Daniel P.
dc.contributor.mitauthorDrennan, Catherine L.
dc.relation.journalBiochimica et Biophysica Acta (BBA) - Proteins and Proteomicsen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsDowling, Daniel P.; Vey, Jessica L.; Croft, Anna K.; Drennan, Catherine L.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-5486-2755
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen_US


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