title: SPASM and twitch domains in S-adenosylmethionine (SAM) radical enzymes.
abstract: S-Adenosylmethionine (SAM, also known as AdoMet) radical enzymes use SAM and a [4Fe-4S] cluster to catalyze a diverse array of reactions. They adopt a partial triose-phosphate isomerase (TIM) barrel fold with N- and C-terminal extensions that tailor the structure of the enzyme to its specific function. One extension, termed a SPASM domain, binds two auxiliary [4Fe-4S] clusters and is present within peptide-modifying enzymes. The first structure of a SPASM-containing enzyme, anaerobic sulfatase-maturating enzyme (anSME), revealed unexpected similarities to two non-SPASM proteins, butirosin biosynthetic enzyme 2-deoxy-scyllo-inosamine dehydrogenase (BtrN) and molybdenum cofactor biosynthetic enzyme (MoaA). The latter two enzymes bind one auxiliary cluster and exhibit a partial SPASM motif, coined a Twitch domain. Here we review the structure and function of auxiliary cluster domains within the SAM radical enzyme superfamily.
authors.affiliation: From the Departments of Chemistry and.
authors.forename: Tsehai A J
authors.initials: TA
authors.lastname: Grell
authors.affiliation: From the Departments of Chemistry and.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goldman
authors.affiliation: From the Departments of Chemistry and Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 cdrennan@mit.edu.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D000818:Animals; D003067:Coenzymes / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008667:Metalloproteins / Q000378:metabolism*; D008745:Methylation; D000090006:Molybdenum Cofactors; D011496:Protein Methyltransferases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011621:Pteridines / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism*; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*
chemical_list: D003067:Coenzymes; D005609:Free Radicals; D007506:Iron-Sulfur Proteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011496:Protein Methyltransferases; D011621:Pteridines; D012436:S-Adenosylmethionine; D013429:Sulfatases; D014305:Triose-Phosphate Isomerase; C022261:molybdopterin
keywords: AdoMet; Iron-Sulfur Protein; Post-translational Modification (PTM); Radical; S-Adenosylmethionine (SAM); Structural Biology