Arabinosyltransferase complex (EmbA-EmbB-EmbC) (EmbABC)

The Arabinosyltransferase complex, comprising the EmbA, EmbB, and EmbC proteins, is a vital enzymatic system in Mycobacterium tuberculosis (Mtb) responsible for the biosynthesis of the mycobacterial cell wall (Zhang et al., 2020). Specifically, the EmbA-EmbB heterodimer catalyzes the synthesis of the arabinan domain of arabinogalactan (AG), while the EmbC homodimer is responsible for the arabinan domain of lipoarabinomannan (LAM) (Goude et al., 2009). These components are essential for the structural integrity and virulence of the pathogen. The complex is the primary target of the first-line anti-tuberculosis drug ethambutol, which mimics the substrate and occupies the active site of the enzymes (Tan et al., 2020). Inhibition of these enzymes leads to the accumulation of the precursor decaprenyl-phospho-arabinose and the cessation of cell wall assembly. Resistance to ethambutol is most commonly associated with mutations in the embB gene, particularly at the Met306 position (Sreevatsan et al., 1997). Given the rise of drug-resistant TB, the Arabinosyltransferase complex remains a high-priority target for the development of novel therapeutics.

Other names

EmbA-EmbB complexEmbC-EmbC complexMycobacterial arabinosyltransferaseArabinosyltransferase A/B/CEmbCAB complex

Ethambutol acts as a bacteriostatic agent by inhibiting the arabinosyltransferase enzymes (EmbA, EmbB, and EmbC). It functions as a substrate analog that competes with the acceptor substrate for binding at the active site, thereby blocking the polymerization of D-arabinofuranose into the arabinan segments of arabinogalactan and lipoarabinomannan (Tan et al., 2020). This disruption of cell wall synthesis increases cell wall permeability and eventually leads to bacterial cell death.