title: Radical SAM activation of the B12-independent glycerol dehydratase results in formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'-deoxyadenosine.
abstract: Activation of glycyl radical enzymes (GREs) by S-adenosylmethonine (AdoMet or SAM)-dependent enzymes has long been shown to proceed via the reductive cleavage of SAM. The AdoMet-dependent (or radical SAM) enzymes catalyze this reaction by using a [4Fe-4S] cluster to reductively cleave AdoMet to form a transient 5'-deoxyadenosyl radical and methionine. This radical is then transferred to the GRE, and methionine and 5'-deoxyadenosine are also formed. In contrast to this paradigm, we demonstrate that generation of a glycyl radical on the B(12)-independent glycerol dehydratase by the glycerol dehydratase activating enzyme results in formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'-deoxyadenosine. This demonstrates for the first time that radical SAM activases are also capable of an alternative cleavage pathway for SAM.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Demick
authors.forename: William N
authors.initials: WN
authors.lastname: Lanzilotta
mesh_terms: D002384:Catalysis; D003839:Deoxyadenosines / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D005609:Free Radicals / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism*; D008715:Methionine / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D012436:S-Adenosylmethionine / Q000737:chemistry* / Q000502:physiology; D013872:Thionucleosides / Q000737:chemistry / Q000378:metabolism*; D014805:Vitamin B 12 / Q000737:chemistry / Q000502:physiology*
chemical_list: D003839:Deoxyadenosines; D005609:Free Radicals; D013872:Thionucleosides; C033714:5'-deoxyadenosine; C008500:5'-methylthioadenosine; D012436:S-Adenosylmethionine; D008715:Methionine; D006836:Hydro-Lyases; C020671:glycerol dehydratase; D014805:Vitamin B 12; D005998:Glycine