肺炎克雷伯菌5-羟基异脲酸水解酶作用机制的结构与动力学见解
Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae.
作者信息
French Jarrod B, Ealick Steven E
机构信息
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
出版信息
Acta Crystallogr D Biol Crystallogr. 2011 Aug;67(Pt 8):671-7. doi: 10.1107/S090744491101746X. Epub 2011 Jul 12.
Abstract
The stereospecific oxidative degradation of uric acid to (S)-allantoin has recently been demonstrated to proceed via two unstable intermediates and requires three separate enzymatic reactions. The second step of this reaction, the conversion of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, is catalyzed by HIU hydrolase (HIUH). The high-resolution crystal structure of HIUH from the opportunistic pathogen Klebsiella pneumoniae (KpHIUH) has been determined. KpHIUH is a homotetrameric protein that, based on sequence and structural similarity, belongs to the transthyretin-related protein family. In addition, the steady-state kinetic parameters for this enzyme and four active-site mutants have been measured. These data provide valuable insight into the functional roles of the active-site residues. Based upon the structural and kinetic data, a mechanism is proposed for the KpHIUH-catalyzed reaction.
摘要
最近已证明尿酸向（S）-尿囊素的立体特异性氧化降解过程通过两种不稳定的中间体进行，并且需要三个独立的酶促反应。该反应的第二步，即5-羟基异尿酸（HIU）转化为2-氧代-4-羟基-4-羧基-5-脲基咪唑啉，由HIU水解酶（HIUH）催化。已确定了来自机会致病菌肺炎克雷伯菌（KpHIUH）的HIUH的高分辨率晶体结构。KpHIUH是一种同四聚体蛋白，基于序列和结构相似性，属于转甲状腺素蛋白相关蛋白家族。此外，还测量了该酶和四个活性位点突变体的稳态动力学参数。这些数据为活性位点残基的功能作用提供了有价值的见解。基于结构和动力学数据，提出了KpHIUH催化反应的机制。
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