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Mycobacterial cell wall arabinosyltransferase

Molecular classification
Enzyme, Glycosyltransferase
01

Overview

Mycobacterial cell wall arabinosyltransferase refers to a family of membrane-bound glycosyltransferase enzymes critical for the biosynthesis of the complex cell envelope in mycobacteria, including Mycobacterium tuberculosis. These enzymes (notably AftA, AftB, EmbA, EmbB, EmbC, and AftD) catalyze the transfer of arabinofuranose from the lipid donor decaprenyl-phosphate-arabinose to specific acceptor polysaccharides, primarily arabinogalactan and lipoarabinomannan, which are key structural and functional components of the mycobacterial cell wall[1][2][3][4][5][6]. The integrity of this cell wall is essential for bacterial viability, pathogenicity, and resistance to external insults, including antibiotics. Inhibition of these enzymes, particularly by the anti-tuberculosis drug ethambutol, leads to impaired cell wall assembly, loss of envelope integrity, and bacterial death; resistance commonly arises due to mutations in the genes encoding these enzymes[4][6]. This enzyme family is considered a central target for tuberculosis drug discovery due to their essentiality and unique presence in mycobacteria[4][5][6].

Other names
ArabinosyltransferaseMycobacterial arabinofuranosyltransferaseAftAAftBEmbAEmbBEmbC
02

Mechanism of action

Inhibition of arabinosyltransferase activity, prevention of arabinose incorporation into arabinogalactan and lipoarabinomannan, disruption of cell wall synthesis

03

Biological functions

Cell wall biosynthesisPolysaccharide assemblyMaintenance of envelope integrityProtection against host immune defenses
04

Disease associations

InfectionTuberculosisAntimicrobial resistance
05

Safety considerations

Emergence of drug resistance (notable for ethambutol)essential host-pathogen specificity (host toxicity generally low)
06

Interacting drugs

Ethambutol

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