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Mycobacterial arabinosyltransferase EmbC is a membrane-bound enzyme essential for the biosynthesis of lipoarabinomannan (LAM), a critical lipoglycan component of the Mycobacterium tuberculosis cell wall. Unlike its counterparts EmbA and EmbB, which are primarily responsible for the synthesis of the arabinan core of arabinogalactan, EmbC specifically catalyzes the polymerization of arabinose units onto lipomannan to form LAM (Source: UniProt P9WNJ9, PubMed PMID: 15659681). LAM plays a vital role in the structural integrity of the cell envelope and acts as a potent immunomodulator during infection, facilitating the survival of the pathogen within host macrophages. EmbC is a primary target of the first-line antitubercular drug ethambutol, which mimics the substrate decaprenyl-phospho-arabinose to competitively inhibit the enzyme (Source: PubMed PMID: 32555463). Disruption of EmbC activity leads to truncated LAM structures, compromising the bacterial cell wall and enhancing the efficacy of other antibiotics.
Ethambutol acts as a bacteriostatic agent by inhibiting the arabinosyltransferase activity of EmbC, EmbA, and EmbB, which prevents the polymerization of arabinose into the arabinan domains of lipoarabinomannan and arabinogalactan, leading to cell wall defects and increased permeability (Source: PubMed PMID: 32555463, 29401559).
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