Glatigny A, Scazzocchio C
Institut de Génétique et Microbiologie, Unité Associtée au CNRS 1354, Université Paris-Sud, Centre d'Orsay, France.
J Biol Chem. 1995 Feb 24;270(8):3534-50. doi: 10.1074/jbc.270.8.3534.
We have cloned and sequenced the hxA gene coding for the xanthine dehydrogenase (purine hydroxylase I) of Aspergillus nidulans. The gene codes for a polypeptide of 1363 amino acids. The sequencing of a nonsense mutation, hxA5, proves formally that the clones isolated correspond to the hxA gene. The gene sequence is interrupted by three introns. Similarity 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 useful outclass for the other known sequences, which are all from metazoans. In particular, it gives added significance to the missense mutations sequenced in Drosophila melanogaster and leads to the conclusion that while one of the recently sequenced human genes codes for a xanthine dehydrogenase, the other one must code for a different molybdenum-containing hydroxylase, possibly an aldehyde oxidase. The transcription of the hxA gene is induced by the uric acid analogue 2-thiouric acid and repressed by ammonium. Induction necessitates the product of the uaY regulatory gene.
我们已经克隆并测序了构巢曲霉黄嘌呤脱氢酶（嘌呤羟化酶I）的编码基因hxA。该基因编码一个由1363个氨基酸组成的多肽。对无义突变体hxA5的测序正式证明所分离的克隆对应于hxA基因。该基因序列被三个内含子打断。相似性搜索揭示了两个铁硫中心和一个NAD/FAD结合结构域，并确定了钼辅因子结合结构域的共有序列。构巢曲霉的序列对于所有来自后生动物的其他已知序列来说是一个有用的外类群。特别是，它赋予了在黑腹果蝇中测序的错义突变更多意义，并得出结论：虽然最近测序的一个人类基因编码黄嘌呤脱氢酶，但另一个基因必定编码一种不同的含钼羟化酶，可能是醛氧化酶。hxA基因的转录由尿酸类似物2-硫代尿酸诱导，并被铵抑制。诱导需要uaY调控基因的产物。
