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

	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
刊名	theoretical chemistry accounts
	2013-09-01
卷号	132 期号:9
关键词	Lysine Methylornithine Reaction mechanism QM/MM Methylornithine synthase (PylB)
ISSN号	1432-881x
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.
中文摘要	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.
英文摘要	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.
WOS标题词	science & technology ; physical sciences
类目[WOS]	chemistry, physical
研究领域[WOS]	chemistry
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
WOS记录号	WOS:000322595900006
公开日期	2014-05-09
内容类型	期刊论文
源URL	[http://ir.nwipb.ac.cn/handle/363003/3930]
专题	西北高原生物研究所_中国科学院西北高原生物研究所
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. 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.(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).