A QM/MM study of the catalytic mechanism of aspartate ammonia lyase

NWIPB OpenIR

	A QM/MM study of the catalytic mechanism of aspartate ammonia lyase
	Zhang, Jing 1,2; Liu, Yongjun 2,3
	2014-06-01
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING
ISSN	1093-3263
卷号	51 页码:113-119
文章类型	Article
摘要	Aspartate ammonia lyase (Asp) is one of three types of ammonia lyases specific for aspartate or its derivatives as substrates, which catalyzes the reversible reaction of L-aspartate to yield fumarate and ammonia. In this paper, the catalytic mechanism of Asp has been studied by using combined quantum-mechanical/molecular-mechanical (QM/MM) approach. The calculation results indicate that the overall reaction only contains two elementary steps. The first step is the abstraction of C-beta proton of L-aspartate by Ser318, which is calculated to be rate limiting. The second step is the cleavage of C alpha-N bond of L-aspartate to form fumarate and ammonia. Ser318 functions as the catalytic base, whereas His188 is a dispensable residue, but its protonation state can influence the active site structure and the existing form of leaving amino group, thereby influences the activity of the enzyme, which can well explain the pH dependence of enzymatic activity. Mutation of His188 to Ala only changes the active site structure and slightly elongates the distance of C-beta proton of substrate with Ser318, causing the enzyme to remain significant but reduced activity. (C) 2014 Elsevier Inc. All rights reserved.; Aspartate ammonia lyase (Asp) is one of three types of ammonia lyases specific for aspartate or its derivatives as substrates, which catalyzes the reversible reaction of L-aspartate to yield fumarate and ammonia. In this paper, the catalytic mechanism of Asp has been studied by using combined quantum-mechanical/molecular-mechanical (QM/MM) approach. The calculation results indicate that the overall reaction only contains two elementary steps. The first step is the abstraction of C-beta proton of L-aspartate by Ser318, which is calculated to be rate limiting. The second step is the cleavage of C alpha-N bond of L-aspartate to form fumarate and ammonia. Ser318 functions as the catalytic base, whereas His188 is a dispensable residue, but its protonation state can influence the active site structure and the existing form of leaving amino group, thereby influences the activity of the enzyme, which can well explain the pH dependence of enzymatic activity. Mutation of His188 to Ala only changes the active site structure and slightly elongates the distance of C-beta proton of substrate with Ser318, causing the enzyme to remain significant but reduced activity. (C) 2014 Elsevier Inc. All rights reserved.
关键词	Aspartate Ammonia Lyase Qm/mm Mutation Reaction Mechanism L-aspartate
WOS标题词	Science & Technology ; Life Sciences & Biomedicine ; Technology ; Physical Sciences
关键词[WOS]	BACILLUS SP YM55-1 ; SITE-DIRECTED MUTAGENESIS ; MOLECULAR-DYNAMICS ; ESCHERICHIA-COLI ; ARGININOSUCCINATE LYASE ; THERMOSTABLE ASPARTASE ; ENZYMATIC MECHANISM ; MUTATIONAL ANALYSIS ; CHEMICAL MECHANISM ; HAFNIA-ALVEI
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Computer Science ; Crystallography ; Mathematical & Computational Biology
WOS类目	Biochemical Research Methods ; Biochemistry & Molecular Biology ; Computer Science, Interdisciplinary Applications ; Crystallography ; Mathematical & Computational Biology
WOS记录号	WOS:000340321900013
引用统计	被引频次：10[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/4224
专题	中国科学院西北高原生物研究所
作者单位	1.Jining Univ, Key Lab Inorgan Chem Univ Shandong, Qufu 273155, Shandong, Peoples R China 2.Chinese Acad Sci, Northwest Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China 3.Shandong Univ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jing,Liu, Yongjun. A QM/MM study of the catalytic mechanism of aspartate ammonia lyase[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2014,51:113-119.
APA	Zhang, Jing,&Liu, Yongjun.(2014).A QM/MM study of the catalytic mechanism of aspartate ammonia lyase.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,51,113-119.
MLA	Zhang, Jing,et al."A QM/MM study of the catalytic mechanism of aspartate ammonia lyase".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 51(2014):113-119.

条目包含的文件		下载所有文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
A QM MM study of the（2157KB）			开放获取	CC BY-NC-SA	浏览下载