Maltosyltransferase GlgE (Streptomyces coelicolor V279S variant) (GlgE (V279S))

Streptomyces coelicolor GlgE1-V279S is a site-directed mutant of the maltosyltransferase enzyme GlgE, specifically engineered to serve as a structural and biochemical surrogate for the Mycobacterium tuberculosis GlgE enzyme (Syson et al., 2011). The V279S mutation replaces a valine residue in the S. coelicolor enzyme with a serine, which is the corresponding residue in the M. tuberculosis ortholog, thereby creating an active site environment that more closely resembles the clinical target (Veis et al., 2014). GlgE is a member of the GH13_3 glycoside hydrolase-like family and plays a critical role in the GlgE pathway, which synthesizes alpha-glucans by utilizing maltose-1-phosphate (M1P) as a substrate. This pathway is essential for the survival of mycobacteria, and its disruption leads to the rapid accumulation of M1P, which is bactericidal due to its proteotoxic and metabolic effects (Kalscheuer et al., 2010). Because the GlgE pathway is entirely absent in humans, this enzyme represents a highly selective target for the development of new antitubercular agents. The S. coelicolor V279S variant is widely used in high-throughput screening and X-ray crystallography to identify and optimize small-molecule inhibitors, such as maltose-1-phosphate analogues, aimed at treating tuberculosis (Veis et al., 2014). Overall, GlgE1-V279S is a vital tool in the development of next-generation antibiotics targeting mycobacterial carbohydrate metabolism.

Other names

Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferaseGlgE1SCO0127 V279SMaltosyltransferase GlgE

Competitive inhibition of maltosyltransferase activity, preventing the elongation of alpha-glucan chains and causing the toxic accumulation of maltose-1-phosphate (M1P).