The bacterial cell wall, together with the peptidoglycan layer, maintains cell shape and provides structural integrity, presenting an important antibiotic target. Peptidoglycan turnover involves the enzyme-mediated cleavage of the bonds in the peptidoglycan mesh, a process that needs to be tightly regulated to avoid detrimental effects. Dörr and colleagues investigated the regulation of the endopeptidase ShyA of Vibrio cholerae and found that ShyA assumes a catalytically active, open form and a closed form that is inactive. Mutations that promote the open form led to toxic effects, in line with the notion that cleavage activity needs to be controlled. The data indicated that the endopeptidase is produced as an inactive precursor, and conformational changes expose the active site. Although the signal that promotes this conformational switch is unknown, such a mechanism may enable the rapid induction of cleavage activity under rapidly changing environmental conditions.