| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
S100 proteins are a multigenic family of low-molecular-weitht. Ca^<2+> -binding proteins comprising 19, members. These proteins undergo a conformational hange by Ca^<2+> -binding and consequently interact with their target proteins. We investigated that two antiallergic drugs, Amtexanox and Cromolyn, bind to S100A12 and S100A13 of the S100 protein family. In this study, we used a newly developed antiallergic drug, Olopatadine, as a ligand for affinity chromatography and, examined binding specificity of the drug to S100 proteins, such as S100A1, S100B, S100L, S100A12, and S100A13, in Ca^<2+> -dependent manner but not to calmodulin. Mutagenesis study showed that amino acid residues 76-85 in S100A1 are necessary for its binding to Olopatadine. In contrast, residues 89-94 were identified as an Amlexanox-binding site in S100A1. Moreover, lopatadine did not competitively inhibit S100A1 target protein's blinding site peptides to S100A1. These results indicate that C-terminal region of S100A1 is important for antiallergic drug binding, although the drug binding sites are different according to each antiallergic drag: Differences in the binding sites of S100A1 to antiallergic drugs suggested that the regulatory functions of S100 proteins may exist in several regions. Therefore, these drugs may serve as useful tools for evaluating the physiological significance of S100 protein family.
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