7BWR

Mycobacterium smegmatis arabinosyltransferase complex EmbB2-AcpM2 in substrate DPA bound asymmetric "active state"

7BWR の概要

• エントリーDOI: 10.2210/pdb7bwr/pdb
• EMDBエントリー: 30234
• 分子名称: Integral membrane indolylacetylinositol arabinosyltransferase EmbB, Meromycolate extension acyl carrier protein, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: mycobacterium tuberculosis, embb, cryo-em, ethambutol, cell wall synthesis, arabinoglacatan, arabinosyltransferase, acyl-carrier-protein, transferase
• 由来する生物種: Mycolicibacterium smegmatis MC2 155; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 256179.69

構造登録者

Gao, R.G.,Zhang, L.,Wang, Q.,Rao, Z.H. (登録日: 2020-04-15, 公開日: 2020-05-27, 最終更新日: 2024-03-27)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.5 Å)