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 ; Liu, Yongjun ; Zhang, Rui ; Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.
刊名	THEORETICAL CHEMISTRY ACCOUNTS ; Zhu, WY; Liu, YJ; Zhang, R.QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB),THEORETICAL CHEMISTRY ACCOUNTS,2013,132(9):
	2013-09-01
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.; 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.
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
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, Zhu, WY; Liu, YJ; Zhang, R.QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB),THEORETICAL CHEMISTRY ACCOUNTS,2013,132(9):,2013.
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.
MLA	Zhu, Wenyou,et al."QM/MM study of the conversion mechanism of lysine to methylornithine catalyzed by methylornithine synthase (PylB)".THEORETICAL CHEMISTRY ACCOUNTS (2013).