CLONING AND MOLECULAR CHARACTERIZATION OF HXA, THE GENE CODING FOR THE XANTHINE DEHYDROGENASE (PURINE HYDROXYLASE-I) OF ASPERGILLUS-NIDULANS

We have cloned and sequenced the hxA gene coding for the xanthine dehy drogenase (purine hydroxylase I) of Aspergillus nidulans. The gene cod es for a polypeptide of 1363 amino acids. The sequencing of a nonsense mutation, hxA5, proves formally that the clones isolated correspond t o the hxA gene. The gene sequence is interrupted by three introns. Sim ilarity searches reveal two iron-sulfur centers and a NAD/FAD-binding domain and have enabled a consensus sequence to be determined for the molybdenum cofactor-binding domain. The A. nidulans sequence is a usef ul outclass for the other known sequences, which are all from metazoan s. In particular, it gives added significance to the missense mutation s sequenced in Drosophila melanogaster and leads to the conclusion tha t while one of the recently sequenced human genes codes for a xanthine dehydrogenase, the other one must code for a different molybdenum-con taining hydroxylase, possibly an aldehyde oxidase. The transcription o f the hxA gene is induced by the uric acid analogue 2-thiouric acid an d repressed by ammonium. Induction necessitates the product of the uaY regulatory gene.