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Arabinofuranosyltransferase EmbC (EmbC) is a membrane-bound enzyme belonging to the glycosyltransferase C superfamily, primarily found in mycobacteria such as Mycobacterium tuberculosis (UniProt, 2024; InterPro, 2024). It plays a critical role in the biosynthesis of the mycobacterial cell wall by catalyzing the polymerization of the arabinan domain of lipoarabinomannan (LAM), a key lipoglycan involved in host-pathogen interactions and immune modulation (NIH, 2014; PubMed, 2009). Unlike its counterparts EmbA and EmbB, which are mainly involved in arabinogalactan synthesis, EmbC is specifically dedicated to LAM assembly (Nature, 2020; NIH, 2014). As an essential gene in M. tuberculosis, EmbC is a validated therapeutic target for the frontline antitubercular drug ethambutol, which inhibits its activity and leads to cell wall instability and bacterial death (FDA, 2024; PubMed, 2009). Mutations in the embC gene or the broader embCAB operon are frequently associated with ethambutol resistance in clinical isolates (NIH, 2019; PubMed, 2009). Understanding the structure and function of EmbC is vital for developing next-generation antitubercular agents that can overcome existing resistance mechanisms (ResearchGate, 2011; NIH, 2022).
Ethambutol inhibits the arabinosyltransferase activity of EmbC by competing with the donor substrate decaprenylphosphoryl-arabinose (DPA), thereby blocking the synthesis of lipoarabinomannan (LAM) and disrupting the mycobacterial cell wall (NIH, 2014; PubMed, 2009).
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