Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol

doi:10.1126/science.aba9102

	Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol
	Zhang, Lu1,2,3,4 ; Zhao, Yao1,2,3,5,6 ; Gao, Yan 7; Wu, Lijie1,2,3 ; Gao, Ruogu 6,8,9; Zhang, Qi1,2,3 ; Wang, Yinan1,2,3,6 ; Wu, Chengyao1,2,3 ; Wu, Fangyu 4; Gurcha, Sudagar S.10; Veerapen, Natacha 10; Batt, Sarah M.10; Zhao, Wei 4; Qin, Ling 1,2,3,12; Yang, Xiuna1,2,3 ; Wang, Manfu1,2,3 ; Zhu, Yan1,2,3 ; Zhang, Bing1,2,3 ; Bi, Lijun 8,9; Zhang, Xian'en 8,9; Yang, Haitao1,2,3 ; Guddat, Luke W.11; Xu, Wenqing1,2,3 ; Wang, Quan1,2,3,8,9 ; Li, Jun1,2,3 ; Besra, Gurdyal S.10; Rao, Zihe1,2,3,4,7,8,9
	2020-06-12
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
卷号	368 期号:6496 页码:1211
发表状态	已发表
DOI	10.1126/science.aba9102
摘要	The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as targets for the anti-tuberculosis drug ethambutol. In this study, we determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits arabinosyltransferases by binding to the same site as both substrates in EmbB and EmbC. Most drug-resistant mutations are located near the ethambutol binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and the development of new anti-tuberculosis agents.
收录类别	SCI ; SCIE
资助项目	National Key R&D Program of China[2017YFC0840300] ; Project of International Cooperation and Exchanges NSFC[81520108019] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29020000] ; Medical Research Council[MR/S000542/1]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000544031400026
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS关键词	ACYL CARRIER PROTEIN ; MYCOBACTERIUM-TUBERCULOSIS ; CRYSTAL-STRUCTURES ; ARABINAN BIOSYNTHESIS ; EMBB GENE ; RESISTANCE ; MUTATION ; GLYCOSYLTRANSFERASES ; LIPOARABINOMANNAN ; ARABINOGALACTAN
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/121263
专题	免疫化学研究所_PI研究组_张璐组免疫化学研究所_特聘教授组_饶子和组 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站生命科学与技术学院_硕士生生命科学与技术学院_博士生生命科学与技术学院_PI研究组_许文青组免疫化学研究所_PI研究组_杨海涛组免疫化学研究所_PI研究组_王权组免疫化学研究所_PI研究组_李俊组
共同第一作者	Zhao, Yao
通讯作者	Wang, Quan; Li, Jun; Besra, Gurdyal S.; Rao, Zihe
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 4.Nankai Univ, Coll Life Sci, Coll Pharm, Frontiers Sci Ctr Cell Response,State Key Lab Med, Tianjin 300353, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100101, Peoples R China 7.Tsinghua Univ, Lab Struct Biol, Beijing 100084, Peoples R China 8.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China 9.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Key Lab RNA Biol, Beijing 100101, Peoples R China 10.Univ Birmingham, Inst Microbiol & Infect, Sch Biosci, Birmingham B15 2TT, W Midlands, England 11.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia 12.Univ Oxford, Div Struct Biol, Oxford OX3 7BN, England
第一作者单位	免疫化学研究所; 生命科学与技术学院; iHuman研究所
通讯作者单位	免疫化学研究所; 生命科学与技术学院; iHuman研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Zhang, Lu,Zhao, Yao,Gao, Yan,et al. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol[J]. SCIENCE,2020,368(6496):1211.
APA	Zhang, Lu.,Zhao, Yao.,Gao, Yan.,Wu, Lijie.,Gao, Ruogu.,...&Rao, Zihe.(2020).Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.SCIENCE,368(6496),1211.
MLA	Zhang, Lu,et al."Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol".SCIENCE 368.6496(2020):1211.