Comparison of the sequences of the Aspergillus nidulans hxB and Drosophilamelanogaster ma-I genes with nifS from Azotobacter vinelandii suggests a mechanism for the insertion of the terminal sulphur atom in the molybdopterin cofactor

The molybdopterin cofactor (MoCF) is required for the activity of a variety of oxidoreductases. The xanthine oxidase class of molybdoenzymes requires the MoCF to have a terminal, cyanolysable sulphur ligand. In the sulphite o xidase/nitrate reductase class, an oxygen is present in the same position. Mutations in both the ma-I gene of Drosophila melanogaster and the hxB gene of Aspergillus nidulans result in toss of activities of all molybdoenzymes that necessitate a cyanolysable sulphur in the active centre. The ma-I and hxB genes encode highly similar proteins containing domains common to pyri doxal phosphate-dependent cysteine transulphurases, including the cofactor binding site and a conserved cysteine, which is the putative sulphur donor. Key similarities were found with NifS, the enzyme involved in the generati on of the iron-sulphur centres in nitrogenase. These similarities suggest a n analogous mechanism for the generation of the terminal molybdenum-bound s ulphur ligand. We have identified putative homologues of these genes in a v ariety of organisms, including humans. The human homologue is located in ch romosome 18.q12.