近日，《美国生物化学杂志》（Journal of Biological Chemistry）发表了中科院上海生科院营养科学研究所向嵩研究组的研究论文Structure and function of allophanate hydrolase。该研究解析了脲水解酶（allophanate hydrolase，AH）的三维结构，揭示了它催化反应的机制。
AH分布于多种微生物中，催化脲(allophanate)到氨的转化。AH与尿素羧化酶（urea carboxylase，UC）构成尿素酰胺水解酶（urea amidolyase，UA）复合物，催化尿素到氨的转化，是多种微生物利用尿素作为它们代谢所需氮源的重要环节。尿素是多种含氮的生物分子的代谢产物，使用它为氮源是氮元素在生命圈中的循环的重要环节，但有关AH的三维结构及其在脲(allophanate)催化到氨的具体作用机制尚不清楚。
向嵩研究员指导的博士生研究生樊晨在前期揭示UC的结构和催化反应机理的基础上，通过与营养所尹慧勇组开展合作研究，使用结晶学的方法解析了AH的晶体结构。结果表明：AH由两个催化结构域构成，分别参与两步催化反应中的一步，并揭示了每一步的催化机制。有意思的是，研究发现其中一步反应可能代表一种新颖的脱羧反应。该工作不仅促进了人们对对UA的功能机理及微生物吸取尿素作为氮源等的理解，也拓展了对生物脱羧反应的认识。
该工作得到了国家科技部和中国科学院的经费资助。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Journal of Biological Chemistry doi: 10.1074/jbc.M113.453837
Structure and function of allophanate hydrolase.
Fan C, Li Z, Yin H, Xiang S.
Allophanate hydrolase converts allophanate to ammonium and carbon dioxide. It is conserved in many organisms and is essential for their utilization of urea as a nitrogen source. It also has important functions in a newly discovered eukaryotic pyrimidine nucleic acid precursor degradation pathway, the yeast-hypha transition that several pathogens utilize to escape the host defense, and an s-triazine herbicide degradation pathway recently emerged in many soil bacteria. We have determined the crystal structure of the Kluyveromyces lactis allophanate hydrolase. Together with structure-directed functional studies, we demonstrate that its N and C domains catalyze a two-step reaction and contribute to maintaining a dimeric form of the enzyme required for their optimal activities. Our studies also provide molecular insights into their catalytic mechanism. Interestingly, we found that the C domain probably catalyzes a novel form of decarboxylation reaction that might expand the knowledge of this common reaction in biological systems.
