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Cryo-EM structure of Mycobacterium smegmatis arabinosyltransferase EmbA-EmbB-AcpM2 in complex with ethambutolCryo-EM structure of Mycobacterium smegmatis arabinosyltransferase EmbA-EmbB-AcpM2 in complex with ethambutol
Structural highlights
Function[ACPM_MYCS2] Acyl carrier protein involved in meromycolate extension. Publication Abstract from PubMedThe arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as the targets for the anti-tuberculosis drug ethambutol. We have 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 by binding to the same site as both substrates in EmbB and EmbC. The majority of drug-resistant mutations are located nearby to the ethambutol-binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and development of new anti-tuberculosis agents. 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 SS, Veerapen N, Batt SM, Zhao W, Qin L, Yang X, Wang M, Zhu Y, Zhang B, Bi L, Zhang X, Yang H, Guddat LW, Xu W, Wang Q, Li J, Besra GS, Rao Z Science. 2020 Apr 23. pii: science.aba9102. doi: 10.1126/science.aba9102. PMID:32327601[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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OCA- Indolylacetylinositol arabinosyltransferase
- Large Structures
- Mycolicibacterium smegmatis mc2 155
- Mycs2
- Besra, G S
- Gao, Y
- Li, J
- Rao, Z
- Wang, Q
- Zhang, L
- Zhao, Y
- Acyl carrier protein
- Arabinogalactan
- Arabinosyltransferase
- Cell wall synthesis
- Drug resistance
- Drug target
- Emba
- Embb
- Embc
- Ethambutol
- Lipoarabinomannan
- Mycobacterium smegmati
- Transferase