Lee Youra, Park Byoung Chul, Lee Do Hee, Bae Kwang-Hee, Cho Sayeon, Lee Choong Hwan, Lee Jong Suk, Myung Pyung Keun, Park Sung Goo
Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
Mol Cells. 2006 Oct 31;22(2):141-5.
Uric acid is the end product of the purine degradation pathway in humans. It is catabolized to allantoin by urate oxidase or uricase (E.C. 1.7.3.3.) in most vertebrates except humans, some primates, birds, and certain species of reptiles. Here we provide evidence that mouse transthyretin-related protein facilitates the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Mutagenesis experiments showed that the residues that are absolutely conserved across the TRP family, including His11, Arg51, His102, and the C-terminal Tyr-Arg-Gly-Ser, may constitute the active site of mTRP. Based on these results, we propose that the transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as hydroxyisourate hydrolases.
尿酸是人体嘌呤降解途径的终产物。在除人类、某些灵长类动物、鸟类和某些爬行动物物种之外的大多数脊椎动物中,尿酸通过尿酸氧化酶或尿酸酶(E.C. 1.7.3.3.)分解代谢为尿囊素。在此我们提供证据表明,小鼠转甲状腺素蛋白相关蛋白促进尿酸酶反应的终产物5-羟基异尿酸的水解。诱变实验表明,在TRP家族中绝对保守的残基,包括His11、Arg51、His102以及C端的Tyr-Arg-Gly-Ser,可能构成了mTRP的活性位点。基于这些结果,我们提出,存在于不同生物体中的转甲状腺素蛋白相关蛋白与转甲状腺素蛋白在功能上并无关联,而实际上起着羟基异尿酸水解酶的作用。