Gosset Arabinofuranosyltransferase Overview
Arabinofuranosyltransferases are membrane-associated glycosyltransferase enzymes responsible for the incorporation of arabinofuranosyl residues into pivotal cell wall polysaccharides, especially arabinogalactan (AG) and lipoarabinomannan (LAM), in mycobacteria. Various isoforms (AftA, AftB, AftD, EmbA, EmbB, EmbC) participate in a stepwise assembly process, each with unique roles and acceptor substrate specificity. Their biosynthetic activity is essential for mycobacterial viability, contributes directly to the pathogen’s envelope structure, and is the target of the frontline anti-tubercular drug ethambutol, which inhibits the active site and can be rendered less effective by resistance mutations in these enzymes[1][2][4][5][6][7][8].
Mechanism of Action
Inhibition of cell wall arabinan polymerization, via direct binding to the active site (as with ethambutol) Prevention of arabinofuranosyl residue transfer, disrupting cell wall biosynthesis and integrity
Biological Functions
Disease Associations
Safety Considerations
- Resistance emergence (notable for ethambutol)
- Essentiality for mycobacteria means off-target toxicity for host is low, but clinical safety relies on antimicrobial selectivity
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| Mutations in EmbB, EmbC, AftA, etc., which indicate ethambutol resistance |
| Cell envelope composition (as a functional readout) |