Arabinosyltransferase EmbB (EmbB)

Arabinosyltransferase EmbB is a vital membrane-bound enzyme in Mycobacterium tuberculosis that plays a critical role in the synthesis of the mycobacterial cell wall. It is responsible for the polymerization of arabinose into arabinogalactan (AG) and lipoarabinomannan (LAM), which are essential structural components that provide the bacterium with a protective barrier against environmental stress and host immune responses (UniProt P9WNJ3). EmbB typically functions within a heterotrimeric complex alongside EmbA and EmbC to facilitate the assembly of the mycolyl-arabinogalactan-peptidoglycan complex. This enzyme is the primary molecular target of ethambutol, a first-line antibiotic used in the treatment of tuberculosis. Inhibition of EmbB by ethambutol leads to the cessation of cell wall synthesis and eventual lysis of the mycobacteria. Clinical resistance to ethambutol is frequently linked to specific point mutations in the embB gene, most notably at the Met306 residue, which alters the drug-binding pocket (Safi et al., 2013, Nature Communications).

Other names

Arabinosyltransferase BEthambutol resistance protein BEmbB proteinIntegral membrane arabinosyltransferase EmbB

Ethambutol acts as an antimetabolite that binds to the EmbB enzyme, inhibiting the polymerization of D-arabinofuranose into the arabinogalactan layer of the mycobacterial cell wall. This inhibition disrupts the assembly of the mycolyl-arabinogalactan-peptidoglycan complex, leading to increased cell wall permeability and bacterial cell death (Zhang et al., 2020, Science; Goude et al., 2009, Antimicrobial Agents and Chemotherapy).