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Arabinosyltransferase EmbA-EmbB-EmbC complex is a set of membrane-bound glycosyltransferase enzymes found in mycobacteria (notably Mycobacterium tuberculosis) and is essential for the biosynthesis of their complex cell wall[6][5]. EmbA and EmbB catalyze the branching and polymerization of arabinose residues in arabinogalactan, while EmbC acts on lipoarabinomannan, both key to envelope structure and integrity[2][3][5]. Ethambutol, a frontline anti-tuberculosis drug, inhibits these enzymes by binding competitively at the active site, thereby blocking cell wall arabinan synthesis[6][7][4]. Mutations in embB and embC confer resistance to ethambutol, making these genes important markers in TB molecular diagnostics[1][4][7]. The complex is a paradigm for essential, druggable enzymes in tuberculosis and other mycobacterial infections.
Ethambutol inhibits the arabinosyltransferase activity of EmbA, EmbB, and EmbC by binding to their active site and competing with the natural substrates (decaprenylphosphoryl-D-arabinofuranose and arabinose acceptor chains)[6][1][4][7]. Drug binding prevents the polymerization and branching of arabinan, thereby disrupting cell wall synthesis and integrity[1][6].
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