Peptidoglycan polymerase function and regulation.

Abstract

SUMMARYMost bacterial species possess two distinct types of glycosyltransferases (GTases or GTs), each with unique structural folds, which catalyze the addition of lipid II monomers to the anomeric reducing end of a growing glycan chain, ultimately forming β-1,4 glycosidic bonds. These bonds link the GlcNAc-MurNAc-peptide disaccharide subunits of the peptidoglycan (PG) polymer. The first type belongs to the carbohydrate-active enzyme (CAZy) GT51 family, which includes a lysozyme-like domain typically associated with a transpeptidase domain in bifunctional class A penicillin-binding proteins (aPBPs) and is occasionally found as a monofunctional GTase in certain bacteria. The second type, a C1-type GTase from the CAZy GT119 family, has a distinctly different structural fold and is composed of polytopic membrane proteins. These proteins also belong to the SEDS (shape, elongation, division, and sporulation) family and are characterized by 10 transmembrane segments and a large extracellular loop. In a single bacterial cell, multiple representatives of each family (aPBPs and SEDS) are typically present, often performing semi-redundant or distinct physiological functions. This review focuses on the structure-activity relationship of these two crucial PG GTases, the coordination between their GTase and the transpeptidase activities, and the regulatory mechanisms controlling these enzymes during cell growth and division within the elongasome and divisome complexes.