Cell wall arabinosyltransferase (Emb)

Cell wall arabinosyltransferases, primarily the EmbA, EmbB, and EmbC proteins, are essential glycosyltransferases in Mycobacteria responsible for the assembly of the arabinan segments of the cell wall (Zhang et al., 2020, Science). These enzymes catalyze the transfer of D-arabinofuranose from the donor decaprenyl-phospho-arabinose to the arabinogalactan and lipoarabinomannan components of the mycobacterial cell envelope (Goude et al., 2009, Journal of Biological Chemistry). Arabinogalactan serves as a critical bridge between the peptidoglycan layer and the outer mycolic acids, maintaining the structural integrity and low permeability of the cell wall (Alderwick et al., 2005, Protein Science). Because these enzymes are absent in humans and vital for bacterial survival, they are the primary target of the first-line antitubercular drug ethambutol (DrugBank DB00330). Inhibition of these transferases leads to a weakened cell wall, increased susceptibility to other drugs, and eventual bacterial lysis (Telenti et al., 1997, Nature Medicine). Mutations in the genes encoding these enzymes, particularly embB, are a major mechanism of clinical resistance to ethambutol in Mycobacterium tuberculosis (Safi et al., 2013, Nature Communications).

Other names

ArabinosyltransferaseEmbAEmbBEmbCMycobacterial arabinosyltransferaseArabinosyl transferase

Ethambutol inhibits the arabinosyltransferase enzymes (EmbA, EmbB, and EmbC), which are responsible for the polymerization of arabinose into the arabinan domain of the mycobacterial cell wall (Zhang et al., 2020, Science). This inhibition disrupts the assembly of the arabinogalactan-peptidoglycan complex and the synthesis of lipoarabinomannan, leading to increased cell wall permeability and bacterial death (DrugBank DB00330).