Arabinosyltransferase EmbA, EmbB, and EmbC (EmbA/B/C)

Arabinosyltransferases EmbA, EmbB, and EmbC are membrane-bound enzymes essential for the biosynthesis of the mycobacterial cell wall in Mycobacterium tuberculosis [1]. These enzymes catalyze the transfer of arabinofuranosyl residues from the donor molecule decaprenyl-phospho-arabinose to the arabinan domains of arabinogalactan and lipoarabinomannan [2]. EmbA and EmbB typically function as a heterodimeric complex (EmbAB) responsible for the synthesis of the arabinan core of arabinogalactan, which links the peptidoglycan to the outer mycolic acid layer, providing structural rigidity [2, 4]. EmbC is primarily dedicated to the synthesis of lipoarabinomannan, a lipoglycan critical for host-pathogen interactions and immune modulation [4]. These enzymes are the primary molecular targets of ethambutol, a first-line antitubercular drug [3]. Inhibition of these transferases by ethambutol leads to increased cell wall permeability and bacterial lysis, though clinical resistance frequently arises through mutations in the embB gene [2, 4].

Other names

EmbAEmbBEmbCArabinosyltransferase AArabinosyltransferase BArabinosyltransferase CEthambutol-sensitive arabinosyltransferasesEmbCAB complex

Ethambutol acts as an antimetabolite that binds to the EmbA, EmbB, and EmbC enzymes, specifically inhibiting the polymerization of D-arabinofuranose from the donor decaprenyl-phospho-arabinose into the cell wall arabinan. This inhibition disrupts the assembly of the arabinogalactan-peptidoglycan complex and lipoarabinomannan, compromising the structural integrity of the mycobacterial cell envelope and leading to bacterial death [2, 3].