Mycobacterial arabinosyltransferase complex (EmbA-EmbB-EmbC) (EmbABC)

The Mycobacterial arabinosyltransferase complex is a vital enzymatic assembly in Mycobacterium tuberculosis, primarily composed of the EmbA, EmbB, and EmbC proteins. These membrane-bound glycosyltransferases are responsible for the synthesis of arabinan polymers, which are essential components of the mycobacterial cell wall's arabinogalactan (AG) and lipoarabinomannan (LAM) layers (Goude et al., 2009, Journal of Biological Chemistry, 284(17):11602-11613). Specifically, EmbA and EmbB form a heterodimer involved in AG synthesis, while EmbC functions as a homodimer dedicated to LAM synthesis (Zhang et al., 2020, Science, 368(6496):1211-1219). Because these structures are unique to mycobacteria and critical for maintaining cell wall integrity and virulence, the complex is a major target for anti-tuberculosis therapy. The first-line drug ethambutol specifically targets this complex by mimicking the natural substrate, decaprenyl-phospho-arabinose, thereby halting cell wall assembly and inhibiting bacterial growth (Tan et al., 2020, Nature Communications, 11:3391). Resistance to ethambutol is frequently linked to mutations within the embCAB operon, particularly in the embB gene (Safi et al., 2013, Nature Genetics, 45(10):1190-1197).

Other names

Arabinosyltransferase EmbAArabinosyltransferase EmbBArabinosyltransferase EmbCEmbA-EmbB complexEmbC-EmbC complexEthambutol-sensitive arabinosyltransferase

Ethambutol acts as a bacteriostatic agent by inhibiting the arabinosyltransferase enzymes (EmbA, EmbB, and EmbC), which are responsible for the polymerization of D-arabinofuranose into the arabinogalactan and lipoarabinomannan layers of the mycobacterial cell wall. This inhibition leads to increased cell wall permeability and eventual cell death (Zhang et al., 2020, Science, 368(6496):1211-1219).