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Arabinosyltransferase AftA is a membrane-bound glycosyltransferase enzyme essential for the biosynthesis of the mycobacterial cell wall. It catalyzes the initial transfer ("priming") of an arabinofuranosyl residue from decaprenyl-monophosphoryl-arabinose onto a mature galactan chain, initiating the formation of branched arabinan domains that are critical for constructing the rigid mycolylarabinogalactan-peptidoglycan core. This process is vital for maintaining cell envelope integrity and viability in pathogenic species such as Mycobacterium tuberculosis. The enzyme is a validated therapeutic target; it is inhibited by ethambutol, an important first-line anti-tuberculosis drug. Resistance arises primarily through mutations in genes encoding this and related enzymes within the embCAB operon. Structural studies reveal that AftA functions as a dimer with a conserved GT-C fold and plays an indispensable role at an early step in cell wall polysaccharide assembly.
Inhibition of the enzyme blocks polymerization of arabinogalactan, disrupting cell wall synthesis and leading to bacterial death or growth inhibition.
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