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S100A1: A New Approach to Disease Treatment
Tyler C. Foreman* and Danna B. Zimmer

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4467


Objective: Aberrant regulation of S100A1 signaling occurs in numerous human and veterinary diseases including many types of cancer, neurological disorders, cardiomyopathy and diabetes. This project tests the feasibility of using amino acid sequence analysis to identify S100A1 target proteins with the hopes of ultimately producing novel therapies for disease by directing treatment at the target protein-S100A1 interaction.

Procedure: The National Center for Biotechnology website was used to search the GenBank database for target proteins. Microsoft Word was then used to manually search for known binding sequences in target proteins: a tryptophan anchored amphipathic helix, (K/R)(L/I)XWXX(I/L)L, and a basic alpha helix I motif. The BLAST function was used to search for proteins containing any variation of the tryptophan anchored amphipathic helix.

Results: Four known S100A1 target proteins contained a tryptophan anchored amphipathic helix or a basic alpha helix I motif, while the other 27 did not. Nineteen potential target proteins for S100A1 were produced using the BLAST function. S100A1 was found to potentially regulate two new functions: olfaction and placental function. S100A1 may also be involved in the disease process of albinism.

Conclusions and Clinical Relevance: These results suggest that target proteins utilize multiple motifs to interact with S100A1. Additional biochemical and structural analyses will be needed to identify binding domains. Delineation of the molecular mechanism of S100A1 target protein interactions represents the first step in developing therapeutic agents to normalize S100A1 signaling in human and veterinary diseases.