Structural evidence for lack of inhibition of fish goose-type lysozymes by a bacterial inhibitor of lysozyme

• Published in: Journal of molecular modeling 2008-09, Vol.14 (9), p.777-788
• Main Authors: Kyomuhendo, Peter, Nilsen, Inge W., Brandsdal, Bjørn Olav, Smalås, Arne O.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Computer Simulation; Crystallography; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Expressed Sequence Tags; Fishes; Models, Molecular; Molecular Medicine; Molecular Sequence Data; Molecular Weight; Muramidase - antagonists & inhibitors; Muramidase - chemistry; Muramidase - classification; Original Paper; Phylogeny; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Static Electricity; Surface Properties; Theoretical and Computational Chemistry; Water - chemistry
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-008-0317-9

It is known that bacteria contain inhibitors of lysozyme activity. The recently discovered Escherichia coli inhibitor of vertebrate lysozyme (Ivy) and its potential interactions with several goose-type (g-type) lysozymes from fish were studied using functional enzyme assays, comparative homology modelling, protein–protein docking, and molecular dynamics simulations. Enzyme assays carried out on salmon g -type lysozyme revealed a lack of inhibition by Ivy. Detailed analysis of the complexes formed between Ivy and both hen egg white lysozyme (HEWL) and goose egg white lysozyme (GEWL) suggests that electrostatic interactions make a dominant contribution to inhibition. Comparison of three dimensional models of aquatic g -type lysozymes revealed important insertions in the β domain, and specific sequence substitutions yielding altered electrostatic surface properties and surface curvature at the protein–protein interface. Thus, based on structural homology models, we propose that Ivy is not effective against any of the known fish g-type lysozymes. Docking studies suggest a weaker binding mode between Ivy and GEWL compared to that with HEWL, and our models explain the mechanistic necessity for conservation of a set of residues in g -type lysozymes as a prerequisite for inhibition by Ivy.