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Arabinosyltransferase EmbCAB complex is a group of membrane-associated glycosyltransferase enzymes found in Mycobacterium species. It consists of three key proteins: EmbA, EmbB, and EmbC, each of which has distinct but complementary roles in cell wall biosynthesis. EmbA and EmbB are required for the synthesis and branching of arabinogalactan, while EmbC catalyzes the elongation of lipoarabinomannan. These enzymes transfer arabinose residues from decaprenyl-phosphate-arabinose (DPA) donors to cell wall acceptors, a critical step for cell wall assembly and integrity[1][2][3][4][5]. The EmbCAB complex is the principal target of ethambutol, which binds to a pocket overlapping the donor and acceptor substrate sites, thus competitively inhibiting enzymatic activity and causing cell wall synthesis defects. Mutations in the EmbCAB genes—especially embB—confer resistance to ethambutol and are associated with multidrug-resistant tuberculosis, making this complex a critical focus for antibacterial drug development and resistance surveillance[3][4][5].
Competitive inhibition of arabinosyltransferase active site by ethambutol, which blocks the incorporation of arabinose into cell wall polymers and thus inhibits cell wall formation
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