肺炎克雷伯菌中新型FAD依赖性尿酸氧化酶HpxO的生化特性
Biochemical characterization of the HpxO enzyme from Klebsiella pneumoniae, a novel FAD-dependent urate oxidase.
作者信息
O'Leary Seán E, Hicks Katherine A, Ealick Steven E, Begley Tadhg P
机构信息
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
出版信息
Biochemistry. 2009 Apr 14;48(14):3033-5. doi: 10.1021/bi900160b.
Abstract
The HpxO enzyme from Klebsiella pneumoniae was recently proposed, on the basis of genetic studies, to catalyze the hydroxylation of uric acid to 5-hydroxyisourate as part of the purine catabolic pathway. Its primary sequence suggests that the HpxO catalytic activity depends on a flavin cofactor (FAD), contrasting with all previously studied urate oxidase enzymes, which have no cofactor requirement. Here we demonstrate biochemically that HpxO is an FAD-dependent urate oxidase. Our data are consistent with the proposal that HpxO-bound flavin hydroperoxide is the hydroxylating species. These results confirm the existence of a novel mechanistic paradigm in purine catabolism.
摘要
基于遗传学研究，最近有观点认为，肺炎克雷伯菌中的HpxO酶作为嘌呤分解代谢途径的一部分，可催化尿酸羟基化为5-羟基异尿酸。其一级序列表明，HpxO的催化活性依赖于黄素辅因子（FAD），这与之前所有研究的尿酸氧化酶不同，那些酶不需要辅因子。在这里，我们通过生物化学方法证明HpxO是一种依赖FAD的尿酸氧化酶。我们的数据与以下观点一致：与HpxO结合的黄素氢过氧化物是羟基化物质。这些结果证实了嘌呤分解代谢中一种新的机制模式的存在。
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