| Literature DB >> 32327601 |
Lu Zhang1,2, Yao Zhao1,3,4, Yan Gao5, Lijie Wu1, Ruogu Gao4,6, Qi Zhang1, Yinan Wang1,4, Chengyao Wu1, Fangyu Wu2, Sudagar S Gurcha7, Natacha Veerapen7, Sarah M Batt7, Wei Zhao2, Ling Qin1, Xiuna Yang1, Manfu Wang1, Yan Zhu1, Bing Zhang1, Lijun Bi6, Xian'en Zhang6, Haitao Yang1, Luke W Guddat8, Wenqing Xu1, Quan Wang9,6, Jun Li9, Gurdyal S Besra10, Zihe Rao9,2,5,6.
Abstract
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.Entities:
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Year: 2020 PMID： 32327601 DOI： 10.1126/science.aba9102
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728