近日，《美國生物化學雜志》（Journal of Biological Chemistry）發(fā)表了中科院上海生科院營養(yǎng)科學研究所向嵩研究組的研究論文Structure and function of allophanate hydrolase,。該研究解析了脲水解酶（allophanate hydrolase,，AH）的三維結(jié)構(gòu)，揭示了它催化反應的機制,。
AH分布于多種微生物中,，催化脲(allophanate)到氨的轉(zhuǎn)化。AH與尿素羧化酶（urea carboxylase,，UC）構(gòu)成尿素酰胺水解酶（urea amidolyase,，UA）復合物,，催化尿素到氨的轉(zhuǎn)化,，是多種微生物利用尿素作為它們代謝所需氮源的重要環(huán)節(jié)。尿素是多種含氮的生物分子的代謝產(chǎn)物,，使用它為氮源是氮元素在生命圈中的循環(huán)的重要環(huán)節(jié),，但有關(guān)AH的三維結(jié)構(gòu)及其在脲(allophanate)催化到氨的具體作用機制尚不清楚。
向嵩研究員指導的博士生研究生樊晨在前期揭示UC的結(jié)構(gòu)和催化反應機理的基礎(chǔ)上,，通過與營養(yǎng)所尹慧勇組開展合作研究,，使用結(jié)晶學的方法解析了AH的晶體結(jié)構(gòu)。結(jié)果表明：AH由兩個催化結(jié)構(gòu)域構(gòu)成,，分別參與兩步催化反應中的一步,，并揭示了每一步的催化機制,。有意思的是，研究發(fā)現(xiàn)其中一步反應可能代表一種新穎的脫羧反應,。該工作不僅促進了人們對對UA的功能機理及微生物吸取尿素作為氮源等的理解,，也拓展了對生物脫羧反應的認識。
該工作得到了國家科技部和中國科學院的經(jīng)費資助,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
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.
