Abstract
The bacterial soluble lytic transglycosylase (LT) breaks down the peptidoglycan (PG) layer during processes such as cell division. We present here crystal structures of the soluble LT Cj0843 from Campylobacter jejuni with and without bulgecin A inhibitor in the active site. Cj0843 has a doughnut shape similar but not identical to that of E. coli SLT70. The C-terminal catalytic domain is preceded by an L-domain, a large helical U-domain, a flexible linker, and a small N-terminal NU-domain. The flexible linker allows the NU-domain to reach over and complete the circular shape, using residues conserved in the Epsilonproteobacteria LT family. The inner surface of the Cj0843 doughnut is mostly positively charged including a pocket that has 8 Arg/Lys residues. Molecular dynamics simulations with PG strands revealed a potential functional role for this pocket in anchoring the negatively charged terminal tetrapeptide of the PG during several steps in the reaction including homing and aligning the PG strand for exolytic cleavage, and subsequent ratcheting of the PG strand to enhance processivity in degrading PG strands.
Highlights
The bacterial cell wall of Gram-negative bacteria contains a peptidoglycan (PG) sacculus between the outer and inner membranes
The L-domain is connected to the C-terminal catalytic C-domain
Sequence analysis of other epsilonproteobacteria family lytic transglycosylase (LT) members show that this ring-completing NU-domain interface is conserved (S2 and S4 Figs), suggesting an important functional role
Summary
The bacterial cell wall of Gram-negative bacteria contains a peptidoglycan (PG) sacculus between the outer and inner membranes. The PG is critical to maintain structural and physical integrity of bacteria. The PG layer is a dynamic structure as it needs to be broken down and remodeled during cell growth [1], cell division [2, 3], or during formation of large periplasmspanning structures like flagella or pili [4, 5]. The PG layer is composed of saccharide and amino acid-type building blocks with the saccharide component being a polymer of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc). The PG building block GlcNAc-MurNAc-pentapeptide (part of lipid II) is utilized by transglycosylases to polymerase the PG saccharide chains [6].
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