Arabinofuranosyltransferase EmbA (EmbA)

Arabinofuranosyltransferase EmbA is an essential membrane-bound enzyme in Mycobacterium tuberculosis that belongs to the glycosyltransferase superfamily C (GT-C). It functions as part of the EmbCAB complex, specifically forming a heterodimer with EmbB to catalyze the synthesis of the arabinan domain of arabinogalactan, a critical component of the mycobacterial cell wall. This enzyme is responsible for the formation of the terminal hexaarabinoside motif, which serves as the attachment point for mycolic acids that define the mycobacterial envelope's integrity. Due to its vital role in cell wall assembly and bacterial survival, EmbA is a primary therapeutic target for the first-line antitubercular drug ethambutol. Ethambutol acts by inhibiting the transfer of arabinose residues, leading to a defective cell wall and increased susceptibility to other antibiotics. Mutations in the embA gene or its operon are frequently associated with the development of clinical resistance to ethambutol in tuberculosis patients.

Other names

Arabinosyltransferase AArabinofuranosyltransferase ARv3794EmbA

Ethambutol inhibits the arabinosyltransferase activity of the EmbA-EmbB complex, preventing the polymerization of arabinose from the donor decaprenylphosphoryl-arabinose (DPA) into the arabinan domain of the mycobacterial cell wall, which leads to increased cell wall permeability and bacteriostasis.