5CTV

Catalytic domain of LytA, the major autolysin of Streptococcus pneumoniae, (C60A, H133A, C136A mutant) complexed with peptidoglycan fragment

Summary for 5CTV

• Entry DOI: 10.2210/pdb5ctv/pdb
• Related: 4IVV
• Descriptor: Autolysin, fragment of peptidoglycan, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-methyl 2-acetamido-3-O-[(1R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranoside-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-methyl 2-acetamido-3-O-[(1R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranoside, ... (4 entities in total)
• Functional Keywords: lyta, pneumococci, autolysis, amidase, peptidoglycan complex, antibiotics, hydrolase
• Biological source: Streptococcus pneumoniae serotype 4; More
• Cellular location: Secreted : P06653
• Total number of polymer chains: 3
• Total formula weight: 23181.31

Authors

Achour, A.,Sandalova, T.,Mellroth, P. (deposition date: 2015-07-24, release date: 2016-06-15, Last modification date: 2024-11-06)

Primary citation

Sandalova, T.,Lee, M.,Henriques-Normark, B.,Hesek, D.,Mobashery, S.,Mellroth, P.,Achour, A.
The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity.
Mol.Microbiol., 101:954-967, 2016

PubMed Abstract: The pneumococcal autolysin LytA is a key virulence factor involved in several important functions including DNA competence, immune evasion and biofilm formation. Here, we present the 1.05 Å crystal structure of the catalytic domain of LytA in complex with a synthetic cell-wall-based peptidoglycan (PG) ligand that occupies the entire Y-shaped substrate-binding crevice. As many as twenty-one amino-acid residues are engaged in ligand interactions with a majority of these interactions directed towards the glycan strand. All saccharides are intimately bound through hydrogen bond, van der Waals and CH-π interactions. Importantly, the structure of LytA is not altered upon ligand binding, whereas the bound ligand assumes a different conformation compared to the unbound NMR-based solution structure of the same PG-fragment. Mutational study reveals that several non-catalytic glycan-interacting residues, structurally conserved in other amidases from Gram-positive Firmicutes, are pivotal for enzymatic activity. The three-dimensional structure of the LytA/PG complex provides a novel structural basis for ligand restriction by the pneumococcal autolysin, revealing for the first time an importance of the multivalent binding to PG saccharides.

PubMed: 27273793
DOI: 10.1111/mmi.13435

Experimental method

X-RAY DIFFRACTION (1.05 Å)