Peptidoglycan transglycosylase complex (GTase)

The peptidoglycan transglycosylation complex is a critical enzymatic assembly responsible for the polymerization of the bacterial cell wall. It facilitates the transfer of the disaccharide-pentapeptide moiety from the membrane-anchored precursor, Lipid II, to the growing glycan chain [1][2]. This essential step is performed by two main groups of enzymes: the transglycosylase domains of bifunctional Class A Penicillin-Binding Proteins (aPBPs) and the SEDS (Shape, Elongation, Division, and Sporulation) family proteins, such as RodA and FtsW [1][4]. Because peptidoglycan is absent in eukaryotic cells, this complex represents a highly selective target for antibiotic development [3]. Direct inhibitors like moenomycin bind to the transglycosylase active site, while glycopeptide antibiotics like vancomycin sequester the substrate to prevent its utilization [3]. Inhibition of this complex compromises the structural integrity of the bacterial cell wall, leading to osmotic lysis and cell death [2]. Sources: [1] Meeske, A. J., et al. (2016) Nature; [2] Sauvage, E., et al. (2008) FEMS Microbiology Reviews; [3] Ostash, B., & Walker, S. (2010) Current Opinion in Chemical Biology; [4] Cho, H., et al. (2016) Nature Communications.

Other names

Peptidoglycan polymeraseGlycosyltransferaseClass A Penicillin-Binding Protein (aPBP)SEDS-PBP complexRodA-PBP2 complexFtsW-PBP3 complexLipid II transglycosylase

Inhibition of glycan chain elongation by blocking the transfer of disaccharide-pentapeptide units from Lipid II to the growing peptidoglycan polymer, either through direct enzyme inhibition or substrate sequestration.