InterPro: IPR008335 Eukaryotic molybdopterin oxidoreductase

A number of different eukaryotic oxidoreductases that require and bind a molybdopterin cofactor have been shown [1] to share a few regions of sequence similarity. These enzymes include xanthine dehydrogenase (EC:1.1.1.204), aldehyde oxidase (EC:1.2.3.1), nitrate reductase (EC:1.7.1.1), and sulphite oxidase (EC:1.8.3.1). The multidomain redox enzyme NAD(P)H:nitrate reductase (NR) catalyses the reduction of nitrate to nitrite in a single polypeptide electron transport chain with electron flow from NAD(P)H-FAD-cytochrome b5-molybdopterin-NO(3). Three forms of NR are known, an NADH-specific enzyme found in higher plants and algae (EC:1.7.1.1); an NAD(P)H-bispecific enzyme found in higher plants, algae and fungi (EC:1.7.1.2); and an NADPH-specific enzyme found only in fungi (EC:1.7.1.3) [2]. The mitochondrial enzyme sulphite oxidase (sulphite:ferricytochrome c oxidoreductase; EC:1.8.2.1) catalyses oxidation of sulphite to sulphate, using cytochrome c as the physiological electron acceptor. Sulphite oxidase consists of two structure/function domains, an N-terminal haem domain, similar to cytochrome b5; and a C-terminal molybdopterin domain [3].

Despite functional parallels, members of the family show no sequence similarity to the C-terminal molybdopterin domain of xanthine dehydrogenase, although xanthine dehydrogenase, nitrate reductases and sulphite oxidase all contain the eukaryotic molybdopterin oxidoreductases signature. Sequence comparison suggests that only a single Cys residue (Cys186 in chicken sulphite oxidase), is invariant in all these enzymes, indicating that it may play a role in binding molybdopterin to the protein [4, 5].