Target intelligence / Profile preview

Mycobacterium tuberculosis arabinosyltransferase (AraT)

Target
AraT
Molecular classification
Enzyme, Glycosyltransferase, Glycosyltransferase family 53 (GT53) [8, 12], Membrane protein [1, 12]
01

Overview

Mycobacterium tuberculosis arabinosyltransferases are a family of membrane-associated enzymes essential for the assembly of the complex mycobacterial cell wall. This family includes the Emb proteins (EmbA, EmbB, and EmbC) and the Aft proteins (AftA, AftB, AftC, and AftD), which catalyze the transfer of arabinofuranose from the donor decaprenylphosphoryl-arabinose to the arabinan domains of arabinogalactan and lipoarabinomannan [1, 3, 12]. These polysaccharides form a critical structural barrier that protects the bacterium from environmental stress and antibiotics [2, 20]. The first-line antitubercular drug ethambutol targets the Emb proteins, specifically inhibiting their activity and leading to cell wall disruption and bacterial death [3, 4, 8]. Resistance to ethambutol is frequently associated with mutations in the embB gene, making these enzymes a focal point for monitoring drug efficacy and developing new therapeutic strategies against multidrug-resistant tuberculosis [3, 9, 16].

Other names
Arabinofuranosyltransferase [2, 6, 12]Emb proteins (EmbA, EmbB, EmbC) [3, 11, 15]Aft proteins (AftA, AftB, AftC, AftD) [7, 12]EmbCAB complex [4, 11]
02

Mechanism of action

Inhibition of arabinosyltransferase activity, which prevents the polymerization of arabinose into the cell wall polysaccharides arabinogalactan and lipoarabinomannan, leading to increased cell wall permeability and bacterial growth inhibition [3, 4, 9, 13].

03

Biological functions

Cell wall biogenesis [1, 8]Arabinogalactan (AG) biosynthesis [3, 12]Lipoarabinomannan (LAM) biosynthesis [5, 16]Arabinan polymerization [1, 8]Glycosyltransferase activity [1, 8]
04

Disease associations

Infection (Tuberculosis) [1, 2, 20]
05

Safety considerations

Drug resistance due to mutations in the embB gene [5, 9, 21]Ocular toxicity (optic neuritis) associated with the use of ethambutol, the primary drug targeting these enzymes [4, 9, 13]
06

Interacting drugs

Ethambutol [3, 5, 8, 9]
07

Biomarkers

embB gene mutations (e.g., M306V, M306I) for ethambutol resistance [3, 9, 16]Lipoarabinomannan (LAM) levels in urine or sputum for bacterial burden and treatment response [19, 22]

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