Lytic Glass Cover Removal Tool transglycosylases (LT) are enzymes involved in peptidoglycan (PG) remodeling.However, their contribution to cell-wall-modifying complexes and their potential as antimicrobial drug targets remains unclear.Here, we determined a high-resolution structure of the LT, an outer membrane lipoprotein from Neisseria species with a disordered active site helix (alpha helix 30).
We show that deletion of the conserved alpha-helix 30 interferes with the integrity of the cell wall, disrupts cell division, cell separation, and impairs the fitness of the human pathogen Neisseria meningitidis Hockey Protective - Elbow Pads - Intermediate during infection.Additionally, deletion of alpha-helix 30 results in hyperacetylated PG, suggesting this LtgA variant affects the function of the PG de-O-acetylase (Ape 1).Our study revealed that Ape 1 requires LtgA for optimal function, demonstrating that LTs can modulate the activity of their protein-binding partner.
We show that targeting specific domains in LTs can be lethal, which opens the possibility that LTs are useful drug-targets.