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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
英文关键词	arabinogalactan; arabinose; arabinosyltransferase; decaprenyl phosphate arabinose; ethambutol; transferase; unclassified drug; arabinosyltransferase; ethambutol; glycosyltransferase; tuberculostatic agent; biochemistry; cell component; chemical binding; detection method; drug; drug resistance; enzyme; enzyme activity; inhibition; mutation; amino acid sequence; amino terminal sequence; Archaeoglobus fulgidus; Article; bacterial cell wall; bacterial gene; bacterial growth; bacterial strain; binding site; blue native polyacrylamide gel electrophoresis; Campylobacter lari; carboxy terminal sequence; catalyst; cryoelectron microscopy; Cupriavidus metallidurans; dimerization; embA gene; embB gene; embC gene; enzyme active site; enzyme activity; enzyme inhibition; enzyme mechanism; enzyme substrate; gene deletion; gene frequency; gene locus; gene mutation; immune response; in vitro study; mass spectrometry; Mycobacterium smegmatis; Mycobacterium tuberculosis; nonhuman; polyacrylamide gel electrophoresis; priority journal; protein cross linking; protein function; cell wall; chemistry; enzymology; multidrug resistance; Mycobacterium tuberculosis; protein conformation; Mycobacterium tuberculosis; Antitubercular Agents; Cell Wall; Cryoelectron Microscopy; Drug Resistance, Multiple, Bacterial; Ethambutol; Mycobacterium tuberculosis; Pentosyltransferases; Protein Conformation
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/246153
作者单位	Shanghai Institute for Advanced Immunochemical Studies, iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Response, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin, 300353, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100101, China; Laboratory of Structural Biology, Tsinghua University, Beijing, 100084, China; National Laboratory of Biomacromolecules, Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing, 100101, China; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom; School of Chemistry and Molecular Biosciences, Unive...
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],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.Science,368(6496).
MLA	Zhang L.,et al."Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol".Science 368.6496(2020).