Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein.
Article Details
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Okada M, Tokumitsu H, Kubota Y, Kobayashi R
Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30.
- PubMed ID
- 11944917 [ View in PubMed]
- Abstract
S100 proteins are a multigenic family of low-molecular-weight Ca(2+)-binding proteins comprising 19 members. These proteins undergo a conformational change by Ca(2+)-binding and consequently interact with their target proteins. Recently, we reported that two antiallergic drugs, Amlexanox and Cromolyn, bind to S100A12 and S100A13 of the S100 protein family. In the present study, we used a newly developed antiallergic drug, Olopatadine, as a ligand for affinity chromatography and examined binding specificity of the drug to S100 protein family. Olopatadine binds specifically to S100 proteins, such as S100A1, S100B, S100L, S100A12, and S100A13, in a 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, Olopatadine did not competitively inhibit S100A1-binding site of Amlexanox. Furthermore, we showed that Olopatadine inhibited the binding of S100A1 target protein's binding 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 drug. Differences in the binding sites of S100A1 to antiallergic drugs suggest 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amlexanox Protein S100-A12 Protein Humans UnknownAntagonistDetails Amlexanox Protein S100-A13 Protein Humans UnknownAntagonistDetails Olopatadine Protein S100-A1 Protein Humans UnknownAntagonistDetails Olopatadine Protein S100-A12 Protein Humans UnknownAntagonistDetails Olopatadine Protein S100-A13 Protein Humans UnknownOther/unknownDetails Olopatadine Protein S100-A2 Protein Humans UnknownAntagonistDetails Olopatadine Protein S100-B Protein Humans UnknownOther/unknownDetails