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

PLoS One. 2019 May 9;14(5):e0216427. doi: 10.1371/journal.pone.0216427. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • HCT116 Cells
  • Humans
  • Molecular Docking Simulation*
  • Muramidase* / chemistry
  • Muramidase* / metabolism
  • Neoplasm Proteins* / chemistry
  • Neoplasm Proteins* / metabolism
  • Neoplasms* / chemistry
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Protein Binding
  • Protein Domains
  • Receptor for Advanced Glycation End Products*
  • S100 Calcium Binding Protein A6 / chemistry
  • S100 Calcium Binding Protein A6 / metabolism
  • ortho-Aminobenzoates / pharmacology

Substances

  • AGER protein, human
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Receptor for Advanced Glycation End Products
  • S100 Calcium Binding Protein A6
  • ortho-Aminobenzoates
  • S100A6 protein, human
  • Muramidase
  • tranilast

Grants and funding

This work was supported by the Ministry of Science and Technology (MOST) of Taiwan (grant number MOST 104–2113-M-007-019-MY3, MOST 107–2113-M-007-008), MOST 105-2320-B-039-059-MY3 and MOHW107-TDU-B-212-114025 from Ministry of Health and Welfare (MOHW), and the Drug Development Center, China Medical University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.