Abstract
Human S100A9 (Calgranulin B) is a Ca2+-binding protein from the S100 family that often accompanies human the S100A8 protein (Calgranulin A). S100A9 presents as a homodimer in myeloid cells and emerges as an important mediator during inflammation after calcium binds to its EF hand motifs. Human receptors for the advanced glycation end products (RAGE) protein is one of the target proteins for S100A9 binding to its hydrophobic surface. Interaction between these two proteins will trigger signaling transduction cascades that promote cell growth, proliferation, and tumorigenesis. Here, we solved the solution structure of the mS100A9 homodimer by conducting multi-dimensional NMR experiments. We further characterize the solution interactions between mS100A9 and the RAGE V domain as well as S100A9 with the CHAPS molecule via NMR spectroscopy. Finally, using the HADDOCK program, we demonstrate that CHAPS molecules play a crucial role in blocking the interaction between mS100A9 and the RAGE V domain. WST-1 assay results also support that CHAPS inhibit the bioactivity of mS100A9. This report will help to inform new drug development against cell proliferation.