Arabinofuranosyltransferase B (EmbB) (EmbB)

Arabinofuranosyltransferase B (EmbB) is a membrane-bound enzyme essential for the biosynthesis of the mycobacterial cell wall, specifically the arabinogalactan (AG) component (UniProt P9WNJ1). It belongs to the glycosyltransferase C (GT-C) superfamily and functions as part of a complex, often with EmbA, to catalyze the transfer of arabinose residues from the donor decaprenyl-phosphate-arabinose (DPA) to the growing arabinan chain (Zhang et al., 2020). This activity is crucial for the formation of the terminal hexaarabinoside motif, which provides the structural template for the attachment of mycolic acids, forming the mycolyl-arabinogalactan-peptidoglycan (mAGP) complex (Jankute et al., 2015). EmbB is the primary molecular target of ethambutol, a first-line antibiotic used in the treatment of tuberculosis (Belanger et al., 1996). Ethambutol acts as a competitive inhibitor of DPA, thereby disrupting cell wall assembly and increasing the permeability of the mycobacterial envelope to other drugs (Zhang et al., 2020). Clinical resistance to ethambutol is frequently associated with specific mutations in the embB gene, most notably at the Met306 residue (Telenti et al., 1997).

Other names

Arabinosyltransferase BArabinofuranosyl transferase BEmbB

Ethambutol acts as a competitive inhibitor of the donor substrate decaprenyl-phosphate-arabinose (DPA), binding to the active site of EmbB and preventing the transfer of arabinose residues to the cell wall polysaccharide (Zhang et al., 2020).