Mobley H L, Island M D, Hausinger R P
Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore 21201, USA.
Microbiol Rev. 1995 Sep;59(3):451-80. doi: 10.1128/mr.59.3.451-480.1995.
Urease (urea amidohydrolase; EC 3.5.1.5) catalyzes the hydrolysis of urea to yield ammonia and carbamate. The latter compound spontaneously decomposes to yield another molecule of ammonia and carbonic acid. The urease phenotype is widely distributed across the bacterial kingdom, and the gene clusters encoding this enzyme have been cloned from numerous bacterial species. The complete nucleotide sequence, ranging from 5.15 to 6.45 kb, has been determined for five species including Bacillus sp. strain TB-90, Klebsiella aerogenes, Proteus mirabilis, Helicobacter pylori, and Yersinia enterocolitica. Sequences for selected genes have been determined for at least 10 other bacterial species and the jack bean enzyme. Urease synthesis can be nitrogen regulated, urea inducible, or constitutive. The crystal structure of the K. aerogenes enzyme has been determined. When combined with chemical modification studies, biophysical and spectroscopic analyses, site-directed mutagenesis results, and kinetic inhibition experiments, the structure provides important insight into the mechanism of catalysis. Synthesis of active enzyme requires incorporation of both carbon dioxide and nickel ions into the protein. Accessory genes have been shown to be required for activation of urease apoprotein, and roles for the accessory proteins in metallocenter assembly have been proposed. Urease is central to the virulence of P. mirabilis and H. pylori. Urea hydrolysis by P. mirabilis in the urinary tract leads directly to urolithiasis (stone formation) and contributes to the development of acute pyelonephritis. The urease of H. pylori is necessary for colonization of the gastric mucosa in experimental animal models of gastritis and serves as the major antigen and diagnostic marker for gastritis and peptic ulcer disease in humans. In addition, the urease of Y. enterocolitica has been implicated as an arthritogenic factor in the development of infection-induced reactive arthritis. The significant progress in our understanding of the molecular biology of microbial ureases is reviewed.
脲酶（尿素酰胺水解酶；EC 3.5.1.5）催化尿素水解生成氨和氨基甲酸酯。后一种化合物会自发分解，生成另一分子的氨和碳酸。脲酶表型广泛分布于细菌界，编码该酶的基因簇已从众多细菌物种中克隆出来。包括芽孢杆菌属TB - 90菌株、产气克雷伯菌、奇异变形杆菌、幽门螺杆菌和小肠结肠炎耶尔森菌在内的五个物种的完整核苷酸序列已被测定，长度在5.15至6.45 kb之间。已测定了至少其他10种细菌物种和刀豆脲酶的特定基因序列。脲酶的合成可以受到氮调节、尿素诱导或组成型表达。已确定了产气克雷伯菌脲酶的晶体结构。当与化学修饰研究、生物物理和光谱分析、定点诱变结果以及动力学抑制实验相结合时，该结构为催化机制提供了重要的见解。活性酶的合成需要将二氧化碳和镍离子掺入蛋白质中。已证明辅助基因是激活脲酶脱辅基蛋白所必需的，并提出了辅助蛋白在金属中心组装中的作用。脲酶对于奇异变形杆菌和幽门螺杆菌的毒力至关重要。奇异变形杆菌在尿路中水解尿素直接导致尿石症（结石形成），并促进急性肾盂肾炎的发展。在胃炎实验动物模型中，幽门螺杆菌的脲酶对于胃黏膜定植是必需的，并且是人类胃炎和消化性溃疡疾病的主要抗原和诊断标志物。此外，小肠结肠炎耶尔森菌的脲酶被认为是感染诱导的反应性关节炎发展中的致关节炎因子。本文综述了我们对微生物脲酶分子生物学认识的重大进展。
