5ctv

Publication Abstract from PubMed

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 A 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-pi 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. This article is protected by copyright. All rights reserved.

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.,Sandalova T, Lee M, Henriques-Normark B, Hesek D, Mobashery S, Mellroth P, Achour A Mol Microbiol. 2016 Jun 7. doi: 10.1111/mmi.13435. PMID:27273793^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.