Mycobacterial arabinosyltransferase (Emb) (Emb)

Mycobacterial arabinosyltransferases are a family of membrane-bound glycosyltransferases essential for the biosynthesis of the mycobacterial cell wall. In Mycobacterium tuberculosis, this family consists of three primary enzymes: EmbA, EmbB, and EmbC, which are responsible for the polymerization of arabinose into the arabinogalactan (AG) and lipoarabinomannan (LAM) layers (Zhang et al., 2020, Science). These enzymes utilize decaprenyl-phospho-arabinose (DPA) as the substrate donor to build the branched arabinan structures that provide structural integrity and anchor other components of the cell envelope (Goude et al., 2009, Molecular Microbiology). Because these enzymes are unique to mycobacteria and essential for viability, they are highly effective therapeutic targets. The first-line antitubercular drug ethambutol acts by inhibiting these enzymes, specifically targeting the EmbB and EmbA subunits to disrupt cell wall assembly (Telenti et al., 1997, Nature Medicine). Resistance to ethambutol is most commonly associated with mutations in the embB gene, highlighting the critical role of these enzymes in clinical treatment outcomes (Safi et al., 2013, Nature Communications). Recent structural studies have elucidated the binding mechanism of ethambutol within the active site, providing a basis for the development of next-generation inhibitors (Zhang et al., 2020, Science).

Other names

EmbAEmbBEmbCArabinosyltransferase AArabinosyltransferase BArabinosyltransferase C

Inhibition of arabinosyltransferase activity, which prevents the polymerization of arabinose into the arabinogalactan and lipoarabinomannan layers of the mycobacterial cell wall, leading to increased cell wall permeability and bacterial cell death.