气候变化领域集成服务门户(CCPortal): Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol

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DOI	10.1126/science.aba9102
	Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol
	Zhang L.; Zhao Y.; Gao Y.; Wu L.; Gao R.; Zhang Q.; Wang Y.; Wu C.; Wu F.; Gurcha S.S.; Veerapen N.; Batt S.M.; Zhao W.; Qin L.; Yang X.; Wang M.; Zhu Y.; Zhang B.; Bi L.; Zhang X.; Yang H.; Guddat L.W.; Xu W.; Wang Q.; Li J.; Besra G.S.; Rao Z.
发表日期	2020
ISSN	0036-8075
起始页码	1211
结束页码	1219
卷号	368 期号:6496
英文摘要	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. © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
关键词	biochemistry cell component chemical binding detection method drug drug resistance enzyme enzyme activity inhibition mutation Mycobacterium tuberculosis arabinosyltransferase ethambutol glycosyltransferase tuberculostatic agent cell wall chemistry cryoelectron microscopy enzymology multidrug resistance Mycobacterium tuberculosis protein conformation Antitubercular Agents Cell Wall Cryoelectron Microscopy Drug Resistance, Multiple, Bacterial Ethambutol Mycobacterium tuberculosis Pentosyltransferases Protein Conformation
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133442
推荐引用方式 GB/T 7714	Zhang L.,Zhao Y.,Gao Y.,et al. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol[J]. Science,2020,368(6496).
APA	Zhang L..,Zhao Y..,Gao Y..,Wu L..,Gao R..,...&Rao Z..(2020).Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.,368(6496).
MLA	Zhang L.,et al."Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol".368.6496(2020).