Arabinosyltransferase EmbC (EmbC)

Arabinosyltransferase EmbC is a critical membrane-bound enzyme in Mycobacterium tuberculosis (Mtb) that plays a specialized role in the biosynthesis of the mycobacterial cell envelope. Specifically, EmbC is responsible for the polymerization of the arabinan core of lipoarabinomannan (LAM), a major lipoglycan that modulates the host immune response and is essential for the survival of the pathogen within macrophages (UniProt P9WGI9; PubMed: 15659695). It catalyzes the transfer of D-arabinofuranosyl residues from the donor decaprenyl-monophosphoryl-arabinose (DPA) to growing carbohydrate chains (PubMed: 22493210). As a member of the EmbCAB complex, EmbC is a primary target of the first-line anti-tuberculosis drug ethambutol. Ethambutol inhibits the enzyme by mimicking the DPA substrate, thereby disrupting the assembly of the mycobacterial cell wall and leading to bacterial cell death (PubMed: 32532991). Because EmbC is unique to mycobacteria and absent in humans, it represents a highly specific therapeutic target, although clinical challenges remain regarding the development of drug resistance through genomic mutations in the embCAB operon (PubMed: 28334631).

Other names

Arabinosyltransferase CRv3795embCProbable arabinosyltransferase C

Ethambutol acts as an acceptor analog of the substrate decaprenyl-monophosphoryl-arabinose (DPA), competitively inhibiting the arabinosyltransferase activity of EmbC and preventing the polymerization of arabinose into lipoarabinomannan.