title: Shared function and moonlighting proteins in molybdenum cofactor biosynthesis.
abstract: The biosynthesis of the molybdenum cofactor (Moco) is a highly conserved pathway in bacteria, archaea and eukaryotes. The molybdenum atom in Moco-containing enzymes is coordinated to the dithiolene group of a tricyclic pyranopterin monophosphate cofactor. The biosynthesis of Moco can be divided into three conserved steps, with a fourth present only in bacteria and archaea: (1) formation of cyclic pyranopterin monophosphate, (2) formation of molybdopterin (MPT), (3) insertion of molybdenum into MPT to form Mo-MPT, and (4) additional modification of Mo-MPT in bacteria with the attachment of a GMP or CMP nucleotide, forming the dinucleotide variants of Moco. While the proteins involved in the catalytic reaction of each step of Moco biosynthesis are highly conserved among the Phyla, a surprising link to other cellular pathways has been identified by recent discoveries. In particular, the pathways for FeS cluster assembly and thio-modifications of tRNA are connected to Moco biosynthesis by sharing the same protein components. Further, proteins involved in Moco biosynthesis are not only shared with other pathways, but additionally have moonlighting roles. This review gives an overview of Moco biosynthesis in bacteria and humans and highlights the shared function and moonlighting roles of the participating proteins.
authors.affiliation: .
authors.forename: Silke
authors.initials: S
authors.lastname: Leimkühler
mesh_terms: D000818:Animals; D019843:Archaeal Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003067:Coenzymes / Q000096:biosynthesis*; D006801:Humans; D008667:Metalloproteins / Q000096:biosynthesis*; D000090006:Molybdenum Cofactors; D009943:Organophosphorus Compounds / Q000378:metabolism; D011621:Pteridines; D011622:Pterins / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D003067:Coenzymes; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D009943:Organophosphorus Compounds; D011621:Pteridines; D011622:Pterins; C549445:nulibry; C022261:molybdopterin
keywords: FeS cluster; molybdenum cofactor; molybdoenzymes; moonlighting; sulfur transfer; tRNA thiolation