InterPro domain: IPR005302

Molybdenum cofactor (MOCO) sulphurases [ 1 ] catalyse the insertion of a terminal sulphur ligand into the molybdenum cofactor, thereby converting the oxo form of MOCO to a sulphurylated form. Suphurylated MOCO is required by several enzymes, including: aldehyde oxidase ( 1.2.3.1 ), which function in the last step of abscisic acid biosynthesis in plants [ 2 ]; and xanthine dehydrogenase ( 1.17.1.4 ), which synthesis uric acid from xanthine during nitrogen metabolism [ 3 ].

This entry represents the beta-barrel C-terminal domain of MOCO sulphurase (MOSC domain), which has a beta-barrel structure similar to that of the beta-barrel domain in pyruvate kinase and contains a highly conserved cysteine residue required for activity. MOSC domains are found in several diverse metal-sulphur cluster biosynthesis proteins from both eukaryotes and prokaryotes. MOSC domains occu as either stand-alone forms, such as the YiiM protein from Escherichia coli, or fused to other domains, such as a NifS-like catalytic domain in MOCO sulphurase. The MOSC domain is predicted to be a sulphur-carrier domain that receives sulphur abstracted from pyridoxal phosphate-dependent NifS-like enzymes, on its conserved cysteine, and delivers it for the formation of diverse sulphur-metal clusters [ 4 ].

The MOSC domain contains several patches of hydrophobic residues and an absolutely conserved cysteine residue situated closer to the C-terminal end of the domain. The absolutely conserved cysteine in the MOSC domain is reminiscent of the analogous conservation of a cysteine in the active site of the thioredoxin and rhodanese superfamilies. Members of both these superfamilies, especially of the latter one, have been implicated in the synthesis of Fe-S clusters, through mobilisation of sulphur with their active cysteine.

1. Cell biology of molybdenum. Biochim. Biophys. Acta 1763, 621-35
2. The Arabidopsis LOS5/ABA3 locus encodes a molybdenum cofactor sulfurase and modulates cold stress- and osmotic stress-responsive gene expression. Plant Cell 13, 2063-83
3. Mutations of the silkworm molybdenum cofactor sulfurase gene, og, cause translucent larval skin. Insect Biochem. Mol. Biol. 33, 417-27
4. MOSC domains: ancient, predicted sulfur-carrier domains, present in diverse metal-sulfur cluster biosynthesis proteins including Molybdenum cofactor sulfurases. FEMS Microbiol. Lett. 207, 55-61