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Arabinosyltransferase EmbA (EmbA) is a membrane-bound enzyme in Mycobacterium tuberculosis that plays a pivotal role in the biosynthesis of the mycobacterial cell wall (UniProt: P9WNJ1). It operates within the EmbCAB complex, specifically collaborating with EmbB to catalyze the polymerization of D-arabinofuranose into the arabinogalactan (AG) and lipoarabinomannan (LAM) layers (Zhang et al., 2020, Science). These polysaccharides are essential for maintaining the structural integrity and protective barrier of the bacterium against host immune responses and antibiotics. EmbA is a well-validated therapeutic target, as it is directly inhibited by ethambutol, a cornerstone of first-line tuberculosis treatment (Goude et al., 2009, Antimicrob Agents Chemother). Ethambutol binding disrupts the formation of the terminal hexa-arabinofuranosyl motif, leading to a compromised cell wall and bacterial lysis. Resistance to ethambutol is frequently linked to mutations in the embCAB operon, including the embA promoter region, which can lead to overexpression of the target (Safi et al., 2013, Nat Commun).
Ethambutol inhibits the arabinosyltransferase activity of the EmbCAB complex, specifically blocking the polymerization of arabinose into the arabinogalactan layer of the mycobacterial cell wall.
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