title: Structural studies of molybdopterin synthase provide insights into its catalytic mechanism.
abstract: Molybdenum cofactor biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea, and eukaryotes, including humans. Genetic deficiencies of enzymes involved in cofactor biosynthesis in humans lead to a severe and usually fatal disease. The molybdenum cofactor contains a tricyclic pyranopterin, termed molybdopterin, that bears the cis-dithiolene group responsible for molybdenum ligation. The dithiolene group of molybdopterin is generated by molybdopterin synthase, which consists of a large (MoaE) and small (MoaD) subunit. The crystal structure of molybdopterin synthase revealed a heterotetrameric enzyme in which the C terminus of each MoaD subunit is deeply inserted into a MoaE subunit to form the active site. In the activated form of the enzyme, the MoaD C terminus is present as a thiocarboxylate. The present study identified the position of the thiocarboxylate sulfur by exploiting the anomalous signal originating from the sulfur atom. The structure of molybdopterin synthase in a novel crystal form revealed a binding pocket for the terminal phosphate of molybdopterin, the product of the enzyme, and suggested a binding site for the pterin moiety present in precursor Z and molybdopterin. Finally, the crystal structure of the MoaE homodimer provides insights into the conformational changes accompanying binding of the MoaD subunit.
authors.affiliation: Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, 11794-5215, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rudolph
authors.forename: Margot M
authors.initials: MM
authors.lastname: Wuebbens
authors.forename: Oliver
authors.initials: O
authors.lastname: Turque
authors.forename: K V
authors.initials: KV
authors.lastname: Rajagopalan
authors.forename: Hermann
authors.initials: H
authors.lastname: Schindelin
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013455:Sulfur / Q000737:chemistry; D013466:Sulfurtransferases / Q000737:chemistry*
chemical_list: D013455:Sulfur; D013466:Sulfurtransferases; C085585:molybdopterin synthase