A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from Bacillus subtilis

	A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from Bacillus subtilis
	Yu, YM; Liang, YH; Brostromer, E; Quan, JM; Panjikar, S; Dong, YH; Su, XD; Dong YH(董宇辉)
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2006
卷号	281 期号:48 页码:36929-36936
通讯作者	Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China ; Peking Univ, Shenzhen Grad Sch, Lab Chem Genom, Shenzhen 513055, Peoples R China ; DESY, European Mol Biol Lab, Hamburg Outstn, D-22603 Hamburg, Germany ; Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China
英文摘要	Imidazolonepropionase (EC 3.5.2.7) catalyzes the third step in the universal histidine degradation pathway, hydrolyzing the carbon-nitrogen bonds in 4-imidazolone-5-propionic acid to yield N-formimino-L-glutamic acid. Here we report the crystal structures of the Bacillus subtilis imidazolonepropionase and its complex at 2.0-A resolution with substrate analog imidazole-4-acetic acid sodium (I4AA). The structure of the native enzyme contains two domains, a TIM (triose-phosphate isomerase) barrel domain with two insertions and a small beta-sandwich domain. The TIM barrel domain is quite similar to the members of the alpha/beta barrel metallo-dependent hydrolase superfamily, especially to Escherichia coli cytosine deaminase. A metal ion was found in the central cavity of the TIM barrel and was tightly coordinated to residues His-80, His-82, His-249, Asp-324, and a water molecule. X-ray fluorescence scan analysis confirmed that the bound metal ion was a zinc ion. An acetate ion, 6 A away from the zinc ion, was also found in the potential active site. In the complex structure with I4AA, a substrate analog, I4AA replaced the acetate ion and contacted with Arg-89, Try-102, Tyr-152, His-185, and Glu-252, further defining and confirming the active site. The detailed structural studies allowed us to propose a zinc-activated nucleophilic attack mechanism for the hydrolysis reaction catalyzed by the enzyme.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
研究领域[WOS]	Biochemistry & Molecular Biology
原文出处	SCI
语种	英语
WOS记录号	WOS:000242220800052
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/240205]
专题	高能物理研究所_多学科研究中心
作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Yu, YM,Liang, YH,Brostromer, E,et al. A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from Bacillus subtilis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(48):36929-36936.
APA	Yu, YM.,Liang, YH.,Brostromer, E.,Quan, JM.,Panjikar, S.,...&董宇辉.(2006).A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from Bacillus subtilis.JOURNAL OF BIOLOGICAL CHEMISTRY,281(48),36929-36936.
MLA	Yu, YM,et al."A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from Bacillus subtilis".JOURNAL OF BIOLOGICAL CHEMISTRY 281.48(2006):36929-36936.