Stereospecific recognition of inositol 1,4,5-trisphosphate analogs by the phosphatase, kinase, and binding proteins

Masato Hirata, Fumi Yanaga, Toshitaka Koga, Tomio Ogasawara, Yutaka Watanabe, Shoichiro Ozaki

研究成果: ジャーナルへの寄稿記事

54 引用 (Scopus)

抄録

A series of DL-inositol 1,4,5-trisphosphate (IP3) analogs, with a bulky substituent on the 2nd carbon of the inositol ring, has been synthesized. These compounds exert biological activities with only minor reduction in potency, in several assay systems (Hirata, M., Watanabe, Y., Ishimatsu, T., Ikebe, T., Kimura, Y., Yamaguchi, K., Ozaki, S., and Koga, T. (1989) J. Biol. Chem. 264, 20303-20308). Two analogs with aminocyclohexanecarbonyl (designated as analog 206) or aminobenzoyl group (analog 209) were separated into individual optical isomers and examined for stereospecificity in recognition by IP3-5-phosphatase, IP3-3-kinase and IP3 binding activity. IP3-5-phosphatase activity of erythrocyte ghosts was competitively inhibited by L-209 with a lower Ki value than D-IP3, but with a higher Ki value by L-206. D-Isomers of both analogs at 100 μM failed to inhibit the hydrolysis of D-[3H]IP3. On the other hand, D-isomers but not L-isomers of both analogs were as potent as D-IP3 in the recognition by IP3-3-kinase of rat brain cytosol and only the D-isomer of analog 206 could serve as substrate for the kinase. Also D-isomers of both analogs were equipotent to D-IP3 in displacing [3H]IP3 binding to rat cerebellum microsomes. These observations suggest that the IP3 analogs we synthesized are stereospecifically recognized by three IP3-recognizable proteins, but the phosphatase recognizes opposite isomers. Such being the case, the second hydroxyl group of D-IP3 may be involved in the recognition by IP3-5-phosphatase, but not by IP3-3-kinase and binding sites.

元の言語英語
ページ(範囲)8404-8407
ページ数4
ジャーナルJournal of Biological Chemistry
265
発行部数15
出版物ステータス出版済み - 5 25 1990

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Inositol 1,4,5-Trisphosphate
Phosphoric Monoester Hydrolases
Isomers
Carrier Proteins
Phosphotransferases
Phosphoprotein Phosphatases
Erythrocyte Membrane
Inositol
Microsomes
Rats
Hydroxyl Radical
Cytosol
Cerebellum
Hydrolysis
Carbon
Binding Sites
Bioactivity
Brain
Assays
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

これを引用

Hirata, M., Yanaga, F., Koga, T., Ogasawara, T., Watanabe, Y., & Ozaki, S. (1990). Stereospecific recognition of inositol 1,4,5-trisphosphate analogs by the phosphatase, kinase, and binding proteins. Journal of Biological Chemistry, 265(15), 8404-8407.

Stereospecific recognition of inositol 1,4,5-trisphosphate analogs by the phosphatase, kinase, and binding proteins. / Hirata, Masato; Yanaga, Fumi; Koga, Toshitaka; Ogasawara, Tomio; Watanabe, Yutaka; Ozaki, Shoichiro.

:: Journal of Biological Chemistry, 巻 265, 番号 15, 25.05.1990, p. 8404-8407.

研究成果: ジャーナルへの寄稿記事

Hirata, M, Yanaga, F, Koga, T, Ogasawara, T, Watanabe, Y & Ozaki, S 1990, 'Stereospecific recognition of inositol 1,4,5-trisphosphate analogs by the phosphatase, kinase, and binding proteins', Journal of Biological Chemistry, 巻. 265, 番号 15, pp. 8404-8407.
Hirata, Masato ; Yanaga, Fumi ; Koga, Toshitaka ; Ogasawara, Tomio ; Watanabe, Yutaka ; Ozaki, Shoichiro. / Stereospecific recognition of inositol 1,4,5-trisphosphate analogs by the phosphatase, kinase, and binding proteins. :: Journal of Biological Chemistry. 1990 ; 巻 265, 番号 15. pp. 8404-8407.
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abstract = "A series of DL-inositol 1,4,5-trisphosphate (IP3) analogs, with a bulky substituent on the 2nd carbon of the inositol ring, has been synthesized. These compounds exert biological activities with only minor reduction in potency, in several assay systems (Hirata, M., Watanabe, Y., Ishimatsu, T., Ikebe, T., Kimura, Y., Yamaguchi, K., Ozaki, S., and Koga, T. (1989) J. Biol. Chem. 264, 20303-20308). Two analogs with aminocyclohexanecarbonyl (designated as analog 206) or aminobenzoyl group (analog 209) were separated into individual optical isomers and examined for stereospecificity in recognition by IP3-5-phosphatase, IP3-3-kinase and IP3 binding activity. IP3-5-phosphatase activity of erythrocyte ghosts was competitively inhibited by L-209 with a lower Ki value than D-IP3, but with a higher Ki value by L-206. D-Isomers of both analogs at 100 μM failed to inhibit the hydrolysis of D-[3H]IP3. On the other hand, D-isomers but not L-isomers of both analogs were as potent as D-IP3 in the recognition by IP3-3-kinase of rat brain cytosol and only the D-isomer of analog 206 could serve as substrate for the kinase. Also D-isomers of both analogs were equipotent to D-IP3 in displacing [3H]IP3 binding to rat cerebellum microsomes. These observations suggest that the IP3 analogs we synthesized are stereospecifically recognized by three IP3-recognizable proteins, but the phosphatase recognizes opposite isomers. Such being the case, the second hydroxyl group of D-IP3 may be involved in the recognition by IP3-5-phosphatase, but not by IP3-3-kinase and binding sites.",
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AU - Hirata, Masato

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AU - Ogasawara, Tomio

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