Arabinosyltransferase EmbB and Arabinosyltransferase EmbC (EmbB/EmbC)

Arabinosyltransferase EmbB and Arabinosyltransferase EmbC are essential membrane-bound enzymes in Mycobacterium tuberculosis responsible for the synthesis of the mycobacterial cell wall (UniProt P9WNJ3, P9WNJ1). These enzymes belong to the GT-C family of glycosyltransferases and catalyze the transfer of D-arabinofuranose from the donor molecule decaprenyl-phosphoryl-arabinose to acceptor saccharides (Zhang et al., 2020, Science). EmbB, typically functioning as a heterodimer with EmbA, is primarily involved in the polymerization of the arabinan core of arabinogalactan, while EmbC is essential for the synthesis of lipoarabinomannan (Tan et al., 2020, Science). These processes are vital for maintaining the structural integrity and permeability barrier of the mycobacterial cell envelope. The first-line antitubercular drug ethambutol targets these enzymes by mimicking the arabinose donor, thereby halting cell wall assembly and leading to bacterial cell death (Goude et al., 2009, Antimicrob Agents Chemother). Resistance to ethambutol is frequently mediated by specific mutations within the embB gene, which alter the drug-binding pocket (Safi et al., 2013, Nature Communications).

Other names

EmbBEmbCArabinosyltransferase BArabinosyltransferase CEthambutol-sensitive arabinosyltransferaseArabinosyltransferase EmbBArabinosyltransferase EmbC

Ethambutol acts as a substrate analog that competitively inhibits the arabinosyltransferase activity of EmbB and EmbC by binding to the active site, thereby preventing the polymerization of arabinose into the essential cell wall components arabinogalactan and lipoarabinomannan (Zhang et al., 2020, Science; Goude et al., 2009, Antimicrob Agents Chemother).