6H5F

LtgA disordered Helix

Replaces:  4YP4

Summary for 6H5F

• Entry DOI: 10.2210/pdb6h5f/pdb
• Descriptor: Putative soluble lytic murein transglycosylase (2 entities in total)
• Functional Keywords: peptidoglycan, antibiotic resistance, enzyme hub, transferase
• Biological source: Neisseria meningitidis NM422
• Total number of polymer chains: 1
• Total formula weight: 67824.35

Authors

Williams, A.H. (deposition date: 2018-07-24, release date: 2019-08-28, Last modification date: 2024-11-13)

Primary citation

Williams, A.H.,Wheeler, R.,Deghmane, A.E.,Santecchia, I.,Schaub, R.E.,Hicham, S.,Moya Nilges, M.,Malosse, C.,Chamot-Rooke, J.,Haouz, A.,Dillard, J.P.,Robins, W.P.,Taha, M.K.,Gomperts Boneca, I.
Defective lytic transglycosylase disrupts cell morphogenesis by hindering cell wall de-O-acetylation inNeisseria meningitidis.
Elife, 9:-, 2020

PubMed Abstract: Lytic 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 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 during infection. Additionally, deletion of alpha-helix 30 results in hyperacetylated PG, suggesting this LtgA variant affects the function of the PG de-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.

PubMed: 32022687
DOI: 10.7554/eLife.51247

Experimental method

X-RAY DIFFRACTION (2 Å)