9.B.364. The Putative Arabinosyltransferase B (AraTB) Family These proteins are large (~1100 aas with about 12 - 15 TMSs. 9.B.364.1.1 has 1083 aas and 13 putative TMSs in a 1 (N-terminus) + 12 TMS arrangement followed by a hydrophilic domain. This may be the general topology for the members of this family. The arabinosyltransferases EmbA, EmbB, and EmbC (TC# 9.B.364.1.5) are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as targets for the anti-tuberculosis drug ethambutol. Zhang et al. 2020 determined cryo-EM and x-ray crystal structures of the 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.
References:
Zhang, L., Y. Zhao, Y. Gao, L. Wu, R. Gao, Q. Zhang, Y. Wang, C. Wu, F. Wu, S.S. Gurcha, N. Veerapen, S.M. Batt, W. Zhao, L. Qin, X. Yang, M. Wang, Y. Zhu, B. Zhang, L. Bi, X. Zhang, H. Yang, L.W. Guddat, W. Xu, Q. Wang, J. Li, G.S. Besra, and Z. Rao. (2020). Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Science 368: 1211-1219.
Examples:
TC#	Name	Organismal Type	Example
9.B.364.1.1	Putative arabinosyltransferase B of 1083 aas and 13 putative TM		AraTB of Hoyosella subflava (Amycolicicoccus subflavus)

9.B.364.1.2	Uncharacterized protein of 1050 aas and 13 TMSs in a 1 (N-terminal) + 2 + 2 + 2 + 6 TMS arrangement.		UP of Pseudonocardia autotrophica

9.B.364.1.3	Uncharacterized protein of 1209 aas and 13 TMSs in a 1 + 6 + 6 TMS arrangement.		UP of Quadrisphaera sp. DD2A

9.B.364.1.4	Uncharacterized protein of 995 aas and 15 TMSs in a 1 + 2 + 6 + 6 TMS arrangement.		UP of Saccharomonospora saliphila

9.B.364.1.5	Aarabinosyltransferases, EmbAB and dimeric EmbC, with subunits of 1094, 1098 and 1094 aas, respectively, and all with about 14 TMSs. The structure of the cell wall arabinosyltransferase complex with the anit-tuberculosis drug, ethambutol, bound has been solved (Zhang et al. 2020). The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are targets for the anti-tuberculosis drug ethambutol. Zhang et al. 2020 determined cryo-electron microscopy and x-ray crystal structures of the 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.		EmbAB and EmbC₂ of Mycobacterium tuberculosis