title: Radical S-Adenosylmethionine Enzymes in Human Health and Disease.
abstract: Radical S-adenosylmethionine (SAM) enzymes catalyze an astonishing array of complex and chemically challenging reactions across all domains of life. Of approximately 114,000 of these enzymes, 8 are known to be present in humans: MOCS1, molybdenum cofactor biosynthesis; LIAS, lipoic acid biosynthesis; CDK5RAP1, 2-methylthio-N(6)-isopentenyladenosine biosynthesis; CDKAL1, methylthio-N(6)-threonylcarbamoyladenosine biosynthesis; TYW1, wybutosine biosynthesis; ELP3, 5-methoxycarbonylmethyl uridine; and RSAD1 and viperin, both of unknown function. Aberrations in the genes encoding these proteins result in a variety of diseases. In this review, we summarize the biochemical characterization of these 8 radical S-adenosylmethionine enzymes and, in the context of human health, describe the deleterious effects that result from such genetic mutations.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Landgraf
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Erin L
authors.initials: EL
authors.lastname: McCarthy
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802.|Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802.|The Howard Hughes Medical Institute, The Pennsylvania State University, University Park, Pennsylvania 16802; email: squire@psu.edu.
authors.forename: Squire J
authors.initials: SJ
authors.lastname: Booker
mesh_terms: D019755:Carbon-Carbon Lyases; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006330:Heart Defects, Congenital / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008664:Metal Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D008063:Thioctic Acid / Q000378:metabolism; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism; D000090123:Viperin Protein; D019885:Sulfur Group Transferases; D024101:Mitochondrial Proteins
chemical_list: D019755:Carbon-Carbon Lyases; D051548:Histone Acetyltransferases; D047908:Intracellular Signaling Peptides and Proteins; D007506:Iron-Sulfur Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D012436:S-Adenosylmethionine; D008063:Thioctic Acid; D012359:tRNA Methyltransferases; C444427:RSAD2 protein, human; D000090123:Viperin Protein; C538729:ELP3 protein, human; C405930:CDK5RAP1 protein, human; D019885:Sulfur Group Transferases; D024101:Mitochondrial Proteins; C525110:CDKAL1 protein, human; C114840:MOCS1 protein, human
keywords: Elongator; S-adenosylmethionine; iron–sulfur cluster; lipoic acid; molybdenum cofactor; radicals; tRNA modifications; viperin