Arabinosyltransferase A (EmbA) (EmbA)

Arabinosyltransferase A (EmbA) is a critical enzyme in Mycobacterium tuberculosis responsible for the synthesis of the mycobacterial cell wall (UniProt P9WGI9). It works in concert with EmbB and EmbC as part of a membrane-bound complex to polymerize arabinose into arabinogalactan and lipoarabinomannan, which are essential structural components providing the bacteria with protection and virulence (PubMed: 32322063). EmbA specifically plays a key role in the formation of the alpha-1,3-linked arabinofuranosyl side chains (PubMed: 11790742). This enzyme is a primary target of ethambutol, a first-line antibiotic used in the treatment of tuberculosis (PubChem CID 14052). Ethambutol inhibits the transfer of arabinose units, leading to a weakened cell wall and eventual bacterial death. Mutations in the embA gene, particularly in its promoter region, are frequently associated with clinical resistance to ethambutol (PubMed: 24145533). Understanding the structural biology of EmbA is vital for developing next-generation inhibitors that can overcome existing drug resistance mechanisms.

Other names

EmbAArabinosyltransferase AMycobacterium tuberculosis EmbAEthambutol-sensitive arabinosyltransferase A

Ethambutol acts as an antimetabolite that inhibits the arabinosyltransferase activity of the EmbCAB complex, specifically blocking the polymerization of D-arabinofuranose into the arabinogalactan and lipoarabinomannan components of the mycobacterial cell wall.