Lysozyme as the anti-proliferative agent to block the interaction between S100A6 and the RAGE V domain

• Published in: PloS one Vol. 14; no. 5; p. e0216427
• Main Authors: Khan, Md. Imran, Dowarha, Deepu, Katte, Revansiddha, Chou, Ruey-Hwang, Filipek, Anna, Yu, Chin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2019; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Anthranilic acid; Antiproliferatives; Binding; Biochemistry; Biology and Life Sciences; Blocking; Breast cancer; Cancer cells; Cell cycle; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Chemistry; Complex formation; Enzymes; HCT116 Cells; Humans; Lysozyme; Macrophages; Medicine and Health Sciences; Molecular Docking Simulation; Molecular modelling; Molecular structure; Muramidase - chemistry; Muramidase - metabolism; Neoplasm Proteins - chemistry; Neoplasm Proteins - metabolism; Neoplasms - chemistry; Neoplasms - metabolism; Neoplasms - pathology; NMR; Nuclear magnetic resonance; ortho-Aminobenzoates - pharmacology; Physical Sciences; Physiology; Protein Binding; Protein Domains; Proteins; Receptor for Advanced Glycation End Products; Research and analysis methods; S100 Calcium Binding Protein A6 - chemistry; S100 Calcium Binding Protein A6 - metabolism; Target recognition; China; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216427

In this report, using NMR and molecular modeling, we have studied the structure of lysozyme-S100A6 complex and the influence of tranilast [N-(3, 4-dimethoxycinnamoyl) anthranilic acid], an antiallergic drug which binds to lysozyme, on lysozyme-S100A6 and S100A6-RAGE complex formation and, finally, on cell proliferation. We have found that tranilast may block the S100A6-lysozyme interaction and enhance binding of S100A6 to RAGE. Using WST1 assay, we have found that lysozyme, most probably by blocking the interaction between S100A6 and RAGE, inhibits cell proliferation while tranilast may reverse this effect by binding to lysozyme. In conclusion, studies presented in this work, describing the protein-protein/-drug interactions, are of great importance for designing new therapies to treat diseases associated with cell proliferation such as cancers.