title: The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase.
abstract: The CbiT and CbiE enzymes participate in the biosynthesis of vitamin B12. They are fused together in some organisms to form a protein called CobL, which catalyzes two methylations and one decarboxylation on a precorrin intermediate. Because CbiE has sequence homology to canonical precorrin methyltransferases, CbiT was hypothesized to catalyze the decarboxylation. We herein present the crystal structure of MT0146, the CbiT homolog from Methanobacterium thermoautotrophicum. The protein shows structural similarity to Rossmann-like S-adenosyl-methionine-dependent methyltransferases, and our 1.9 A cocrystal structure shows that it binds S-adenosyl-methionine in standard geometry near a binding pocket that could accommodate a precorrin substrate. Therefore, MT0146/CbiT probably functions as a precorrin methyltransferase and represents the first enzyme identified with this activity that does not have the canonical precorrin methyltransferase fold.
authors.affiliation: Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Keller
authors.forename: Paul M
authors.initials: PM
authors.lastname: Smith
authors.forename: Jordi
authors.initials: J
authors.lastname: Benach
authors.forename: Dinesh
authors.initials: D
authors.lastname: Christendat
authors.forename: George T
authors.initials: GT
authors.lastname: deTitta
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D017014:Methanobacterium / Q000378:metabolism*; D008780:Methyltransferases / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012436:S-Adenosylmethionine / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D012436:S-Adenosylmethionine; D008780:Methyltransferases; C474285:precorrin-8w methyltransferase