EmbCAB arabinosyltransferase complex (EmbCAB) (EmbCAB)

The EmbCAB arabinosyltransferase complex is a critical membrane-associated enzymatic machinery in Mycobacterium tuberculosis, essential for the assembly of the mycobacterial cell wall (Zhang et al., 2020, Science). It is composed of three integral membrane proteins—EmbA, EmbB, and EmbC—which function as glycosyltransferases to catalyze the polymerization of D-arabinofuranose from the donor substrate decaprenyl-phospho-arabinose (DPA) (Tan et al., 2020, Nature Communications). Specifically, the EmbA-EmbB heterodimer is responsible for the synthesis of arabinogalactan, while the EmbC homodimer is primarily involved in the synthesis of lipoarabinomannan (Zhang et al., 2020, Science). These polysaccharides are vital for maintaining the structural integrity and low permeability of the mycobacterial envelope, which protects the pathogen from host immune responses and antibiotics (Goude et al., 2009, Journal of Antimicrobial Chemotherapy). The complex is the primary therapeutic target of ethambutol, a cornerstone of first-line tuberculosis treatment (PubChem, CID 14052). Ethambutol acts as a substrate analog, binding to the active sites of the Emb proteins and competitively inhibiting the polymerization process, which ultimately leads to bacterial cell death (Zhang et al., 2020, Science). Mutations in the embB gene, particularly at the Met306 residue, are the most common mechanism of clinical resistance to ethambutol (Goude et al., 2009, Journal of Antimicrobial Chemotherapy). Recent structural studies have elucidated the binding pocket of ethambutol, providing a blueprint for the design of new inhibitors that can overcome existing resistance mechanisms (Zhang et al., 2020, Science).

Other names

Arabinosyltransferase EmbCABEmbA-EmbB-EmbC complexMycobacterial arabinosyltransferaseArabinosyltransferase A/B/C

Inhibition of arabinosyltransferase activity by competing with the natural substrate decaprenyl-phospho-arabinose (DPA), which prevents the polymerization of arabinose into the essential cell wall components arabinogalactan and lipoarabinomannan (Zhang et al., 2020, Science).