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

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	A QM/MM study of the catalytic mechanism of aspartate ammonia lyase
	Zhang, Jing ; Liu, Yongjun
	2014-06-01
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING ; Zhang, J; Liu, YJ.A QM/MM study of the catalytic mechanism of aspartate ammonia lyase,JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2014,51():113
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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/22088
专题	中国科学院西北高原生物研究所
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, Zhang, J; Liu, YJ.A QM/MM study of the catalytic mechanism of aspartate ammonia lyase,JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2014,51():113,2014.
APA	Zhang, Jing,&Liu, Yongjun.(2014).A QM/MM study of the catalytic mechanism of aspartate ammonia lyase.JOURNAL OF MOLECULAR GRAPHICS & MODELLING.
MLA	Zhang, Jing,et al."A QM/MM study of the catalytic mechanism of aspartate ammonia lyase".JOURNAL OF MOLECULAR GRAPHICS & MODELLING (2014).