7BX8

Mycobacterium smegmatis arabinosyltransferase complex EmbB2-AcpM2 in symmetric "resting state"

Summary for 7BX8

• Entry DOI: 10.2210/pdb7bx8/pdb
• Related: 7BWR
• EMDB information: 30234 30236
• Descriptor: Integral membrane indolylacetylinositol arabinosyltransferase EmbB, Meromycolate extension acyl carrier protein (2 entities in total)
• Functional Keywords: mycobacterium tuberculosis, embb, cryo-em, ethambutol, cell wall synthesis, arabinoglacatan, arabinosyltransferase, acyl-carrier-protein, transferase
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 4
• Total formula weight: 255228.33

Authors

Gao, R.G.,Zhang, L.,Wang, Q.,Rao, Z.H. (deposition date: 2020-04-17, release date: 2020-05-27, Last modification date: 2024-03-27)

Primary citation

Zhang, L.,Zhao, Y.,Gao, R.,Li, J.,Yang, X.,Gao, Y.,Zhao, W.,Gurcha, S.S.,Veerapen, N.,Batt, S.M.,Besra, K.K.,Xu, W.,Bi, L.,Zhang, X.,Guddat, L.W.,Yang, H.,Wang, Q.,Besra, G.S.,Rao, Z.
Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2.
Protein Cell, 11:505-517, 2020

PubMed Abstract: Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

PubMed: 32363534
DOI: 10.1007/s13238-020-00726-6

Experimental method

ELECTRON MICROSCOPY (3.6 Å)