Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH

doi:10.1039/c9ob01996k

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH
	Liu, Bin 1,2; Hou, Yan 5,6; Wang, Xiaozheng 4; Ma, Xiaofang 1,2; Fang, Shiqi 1,2; Huang, Tao 1,2; Chen, Yanli 2; Bai, Zhiqiang 1,2; Lin, Shuangjun 4; Zhang, Rundong 5,6
刊名	ORGANIC & BIOMOLECULAR CHEMISTRY
	2019-11-28
卷号	17 期号:44 页码:9605-9614
ISSN号	1477-0520
DOI	10.1039/c9ob01996k
通讯作者	Lin, Shuangjun(linsj@sjtu.edu.cn) ; Zhang, Rundong(rundongzhang@scu.edu.cn) ; Hu, Kaifeng(kaifenghu@mail.kib.ac.rn)
英文摘要	Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the beta-position of (3R)-beta-methyl-indolepyruvate (MeInPy), forming (3S)-beta-MeInPy. Both compounds are derivatives of l-tryptophan (l-Trp) and are important precursors of bioactive natural products. Here, we report the crystal structures of MarH and the NMR structure of its complex with l-Trp, an analogue of its native substrate, (3R)-beta-MeInPy. Structural analysis and mutagenesis studies indicated that His25 acts as a base to remove H-beta and generate a planar carbanion intermediate, which is then putatively reprotonated on the opposite face by a water molecule to form (3S)-beta-MeInPy in a stereospecific manner. The details of beta-site isomerization at the atomic level provide deeper insights into the epimerization mechanism of MarH and will facilitate further enzyme design to extend the substrate scope.
WOS研究方向	Chemistry
语种	英语
WOS记录号	WOS:000498709600006
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/70684]
专题	昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Lin, Shuangjun; Zhang, Rundong; Hu, Kaifeng
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Key Lab Phytochem & Plant Resources West China, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China 3.Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Chengdu 611137, Sichuan, Peoples R China 4.Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China 5.Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China 6.Sichuan Univ, Dept Ophthalmol, State Key Lab Biotherapy, West China Hosp, Chengdu 610041, Sichuan, Peoples R China
推荐引用方式 GB/T 7714	Liu, Bin,Hou, Yan,Wang, Xiaozheng,et al. Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2019,17(44):9605-9614.
APA	Liu, Bin.,Hou, Yan.,Wang, Xiaozheng.,Ma, Xiaofang.,Fang, Shiqi.,...&Hu, Kaifeng.(2019).Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH.ORGANIC & BIOMOLECULAR CHEMISTRY,17(44),9605-9614.
MLA	Liu, Bin,et al."Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH".ORGANIC & BIOMOLECULAR CHEMISTRY 17.44(2019):9605-9614.