QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB)

doi:10.1007/s00214-013-1385-1

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	QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB)
	Zhu, Wenyou 1; Liu, Yongjun 1,2; Zhang, Rui 3; Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.
	2013-09-01
发表期刊	THEORETICAL CHEMISTRY ACCOUNTS
ISSN	1432-881X
卷号	132 期号:9
文章类型	Article
摘要	Methylornithine synthase (PylB) belongs to the family of radical SAM enzymes which converts (2S)-lysine to (2R,3R)-3-methylornithine in a radical mechanism. In this paper, the mechanism of lysine mutase reaction catalyzed by PylB has been studied by using quantum mechanics/molecular mechanics approach. The calculations reveal that the PylB-catalyzed reaction follows a fragmentation-recombination mechanism involving seven elementary reaction steps. Both the hemolytic cleavage of C alpha-C beta bond of lysine and the ligation of glycyl radical with aminobutene are possible rate limiting, corresponding to the calculated energy barriers of 23.0 and 24.1 kcal/mol, respectively. The intramolecular rotation of a fragment (aminobutene) can well explain the stereochemistry of the final product. Asp 279 functions as a general acid/base, and the other pocket residues such as Asp112, Arg235, and Ser277 form a network of hydrogen bonds responsible for orientation of the substrate.; Methylornithine synthase (PylB) belongs to the family of radical SAM enzymes which converts (2S)-lysine to (2R,3R)-3-methylornithine in a radical mechanism. In this paper, the mechanism of lysine mutase reaction catalyzed by PylB has been studied by using quantum mechanics/molecular mechanics approach. The calculations reveal that the PylB-catalyzed reaction follows a fragmentation-recombination mechanism involving seven elementary reaction steps. Both the hemolytic cleavage of C alpha-C beta bond of lysine and the ligation of glycyl radical with aminobutene are possible rate limiting, corresponding to the calculated energy barriers of 23.0 and 24.1 kcal/mol, respectively. The intramolecular rotation of a fragment (aminobutene) can well explain the stereochemistry of the final product. Asp 279 functions as a general acid/base, and the other pocket residues such as Asp112, Arg235, and Ser277 form a network of hydrogen bonds responsible for orientation of the substrate.
关键词	Lysine Methylornithine Reaction Mechanism Qm/mm Methylornithine Synthase (Pylb)
WOS标题词	Science & Technology ; Physical Sciences
DOI	10.1007/s00214-013-1385-1
关键词[WOS]	DEPENDENT GLUTAMATE MUTASE ; PK(A) VALUES ; S-ADENOSYLMETHIONINE ; AMINO-ACID ; PYRROLYSINE ; DYNAMICS ; DENSITY ; RATIONALIZATION ; BIOSYNTHESIS ; ENZYME
收录类别	SCI
语种	英语
项目资助者	Natural Science Foundation of China(21173129 ; 31200048)
WOS研究方向	Chemistry
WOS类目	Chemistry, Physical
WOS记录号	WOS:000322595900006
引用统计	被引频次：8[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/363003/3930
专题	中国科学院西北高原生物研究所
通讯作者	Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.
作者单位	1.Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, Northwest Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China 3.Ludong Univ, Sch Agr, Yantai 264025, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Wenyou,Liu, Yongjun,Zhang, Rui,et al. QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB)[J]. THEORETICAL CHEMISTRY ACCOUNTS,2013,132(9).
APA	Zhu, Wenyou,Liu, Yongjun,Zhang, Rui,&Liu, YJ .(2013).QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB).THEORETICAL CHEMISTRY ACCOUNTS,132(9).
MLA	Zhu, Wenyou,et al."QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB)".THEORETICAL CHEMISTRY ACCOUNTS 132.9(2013).

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