Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach

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	Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach
	Wang, Kang ; Hou, Qianqian ; Liu, Yongjun ; Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Theoret & Computat Chem Univ Shandong, Jinan 250100, Shandong, Peoples R China.
	2013-11-01
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING ; Wang, K; Hou, QQ; Liu, YJ.Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach,JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2013,46():65-73
摘要	The Taxus canadensis phenylalanine aminomutase (TcPAM) catalyze the isomerization of (S)-alpha-phenylalanine to the (R)-beta-isomer. The active site of TcPAM contains the signature 5-methylene-3,5-dihydroimidazol-4-one (MIO) prosthesis, observed in the ammonia lyase class of enzymes. Up to now, there are two plausible mechanisms for these MIO-dependent enzymes, i.e., the amino-MIO adduct mechanism and the Friedel-Crafts-type reaction mechanism. In response to this mechanistic uncertainty, the phenylalanine aminomutase mechanism was investigated by using density functional methods. The calculation results indicate that: (1) the reaction prefers the amino-MIO adduct mechanism where the 2,3-amine shift process contains six elementary steps; (2) the ammonia elimination step proceeds through an E2 mechanism; (3) a single C1-C alpha bond rotation of 180 degrees in the cinnamate skeleton occurs in the active site prior to the rebinding of NH2 group to the cinnamate. This can be used to explain the stereochemistry of the TcPAM reaction product which is contrary to those of the PaPAM and SgTAM enzymes. Based on these calculations, the roles of important residues in the active site were also elucidated. (C) 2013 Elsevier Inc. All rights reserved.; The Taxus canadensis phenylalanine aminomutase (TcPAM) catalyze the isomerization of (S)-alpha-phenylalanine to the (R)-beta-isomer. The active site of TcPAM contains the signature 5-methylene-3,5-dihydroimidazol-4-one (MIO) prosthesis, observed in the ammonia lyase class of enzymes. Up to now, there are two plausible mechanisms for these MIO-dependent enzymes, i.e., the amino-MIO adduct mechanism and the Friedel-Crafts-type reaction mechanism. In response to this mechanistic uncertainty, the phenylalanine aminomutase mechanism was investigated by using density functional methods. The calculation results indicate that: (1) the reaction prefers the amino-MIO adduct mechanism where the 2,3-amine shift process contains six elementary steps; (2) the ammonia elimination step proceeds through an E2 mechanism; (3) a single C1-C alpha bond rotation of 180 degrees in the cinnamate skeleton occurs in the active site prior to the rebinding of NH2 group to the cinnamate. This can be used to explain the stereochemistry of the TcPAM reaction product which is contrary to those of the PaPAM and SgTAM enzymes. Based on these calculations, the roles of important residues in the active site were also elucidated. (C) 2013 Elsevier Inc. All rights reserved.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/47236
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	Wang, Kang,Hou, Qianqian,Liu, Yongjun,et al. Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, Wang, K; Hou, QQ; Liu, YJ.Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach,JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2013,46():65-73,2013.
APA	Wang, Kang,Hou, Qianqian,Liu, Yongjun,&Liu, YJ .(2013).Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach.JOURNAL OF MOLECULAR GRAPHICS & MODELLING.
MLA	Wang, Kang,et al."Insight into the mechanism of aminomutase reaction: A case study of phenylalanine aminomutase by computational approach".JOURNAL OF MOLECULAR GRAPHICS & MODELLING (2013).