Target intelligence / Profile preview

Arabinosyltransferase AftA (AftA)

Target
AftA
Molecular classification
Enzyme, Glycosyltransferase (specifically GT-C fold family), Membrane-bound enzyme
01

Overview

Arabinosyltransferase AftA is a membrane-bound glycosyltransferase enzyme essential for the biosynthesis of the mycobacterial cell wall. It catalyzes the initial transfer ("priming") of an arabinofuranosyl residue from decaprenyl-monophosphoryl-arabinose onto a mature galactan chain, initiating the formation of branched arabinan domains that are critical for constructing the rigid mycolylarabinogalactan-peptidoglycan core. This process is vital for maintaining cell envelope integrity and viability in pathogenic species such as Mycobacterium tuberculosis. The enzyme is a validated therapeutic target; it is inhibited by ethambutol, an important first-line anti-tuberculosis drug. Resistance arises primarily through mutations in genes encoding this and related enzymes within the embCAB operon. Structural studies reveal that AftA functions as a dimer with a conserved GT-C fold and plays an indispensable role at an early step in cell wall polysaccharide assembly.

Other names
Arabinofuranosyltransferase AftAMycobacterial arabinosyltransferaseAG priming arabinosyltransferase
02

Mechanism of action

Inhibition of the enzyme blocks polymerization of arabinogalactan, disrupting cell wall synthesis and leading to bacterial death or growth inhibition.

03

Biological functions

Cell wall biosynthesis (specifically arabinogalactan assembly)Polymerization of arabinan chains onto galactan in mycobacteriaMaintenance of cell envelope integrity
04

Disease associations

Infection (notably tuberculosis caused by Mycobacterium tuberculosis)
05

Safety considerations

Resistance development due to mutations in the embCAB gene cluster, particularly embB; these mutations can also predispose bacteria to multidrug resistance.Ethambutol toxicity includes ocular neurotoxicity due to off-target effects on mitochondrial function in humans.
06

Interacting drugs

Ethambutol
07

Biomarkers

Mutations in embCAB operon genes (especially embB) are associated with resistance to ethambutol and can serve as biomarkers for drug resistance monitoring.

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