Cloning of the cDNAs coding for two novel molybdo-flavoproteins showing high similarity with aldehyde oxidase and xanthine oxidoreductase

The cDNAs coding for two novel mouse molybdo-flavoproteins, AOH1 and AOH2 ( aldehyde oxidase homolog 1 and 2), were isolated. The AOH1 and AOH2 cDNAs c ode for polypeptides of 1336 amino acids. The two proteins have similar pri mary structure and show striking amino acid identity with aldehyde oxidase and xanthine oxidoreductase, two other molybdo-flavoenzymes. AOH1 and AOH2 contain consensus sequences for a molybdopterin-binding site and two distin ct 2Fe-2S redox centers. In its native conformation, AOH1 has a molecular w eight consistent with a homotetrameric structure. Transfection of the AOH1 and AOH2 cDNAs results in the production of proteins with phenanthridine bu t not hypoxanthine oxidizing activity. Furthermore, the AOH1 protein has be nzaldehyde oxidizing activity with electrophoretic characteristics identica l to those of a previously identified aldehyde oxidase isoenzyme (Holmes, R . S. (1979) Biochem. Genet. 17, 517-528). The AOH1 transcript is expressed in the hepatocytes of the adult and fetal liver and in spermatogonia. In li ver, the AOH1 protein is synthesized in a gender-specific fashion. The expr ession of AOH2 is limited to keratinized epithelia and the basal layer of t he epidermis and hair folliculi. The selective cell and tissue distribution of AOH1 and AOH2 mRNAs is consistent with the localization of the respecti ve protein products.