7BVC

Cryo-EM structure of Mycobacterium smegmatis arabinosyltransferase EmbA-EmbB-AcpM2 in complex with ethambutol

Summary for 7BVC

• Entry DOI: 10.2210/pdb7bvc/pdb
• EMDB information: 30216
• Descriptor: Integral membrane indolylacetylinositol arabinosyltransferase EmbA, Integral membrane indolylacetylinositol arabinosyltransferase EmbB, Meromycolate extension acyl carrier protein, ... (9 entities in total)
• Functional Keywords: mycobacterium smegmatis, cell wall synthesis, drug target, ethambutol, arabinosyltransferase, emba, embb, embc, acyl carrier protein, arabinogalactan, lipoarabinomannan, drug resistance, transferase
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 3
• Total formula weight: 250960.60

Authors

Zhang, L.,Zhao, Y.,Gao, Y.,Wang, Q.,Li, J.,Besra, G.S.,Rao, Z. (deposition date: 2020-04-10, release date: 2020-04-29, Last modification date: 2025-04-09)

Primary citation

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.
Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.
Science, 368:1211-1219, 2020

PubMed Abstract: The arabinosyltransferases EmbA, EmbB, and EmbC are involved in 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.

PubMed: 32327601
DOI: 10.1126/science.aba9102

Experimental method

ELECTRON MICROSCOPY (2.9 Å)