Okadaic acid (OA), a potent inhibitor of type-1 and type-2A protein phosphatases (PP1 and PP2A), has four hydroxyl groups at 2, 7, 24 and 27 positions (see Figure 1). By chemical treatment of OA we synthesized a derivative, in which the 27-hydroxyl group was specifically oxidized (27-dehydro-OA). The inhibitory effect of this OA derivative was examined on the activities of PP1 and PP2A, which were inhibited by intact OA with dissociation constants (Ki) of 150 nM and 32 pM respectively. We found that the affinity of OA was decreased 40-fold (Ki = 6 microM) with PP1 and 230-fold (Ki = 7.3 nM) with PP2A after oxidation of the 27-hydroxyl group. According to the model of the three-dimensional conformation of OA on the basis of X-ray analyses, the 27-hydroxyl group appears to be present in a position relatively free from intramolecular bonding formation, in comparison with the other three hydroxyl groups. The marked increases in the Ki values for PP1 and PP2A, which indicate the reduction of the absolute values of the free energy of binding by 9 kJ/mol and 14 kJ/mol respectively, may imply that the 27-hydroxyl group serves as a binding site with the phosphatase molecules.
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March 1994
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Research Article|
March 01 1994
Affinity of okadaic acid to type-1 and type-2A protein phosphatases is markedly reduced by oxidation of its 27-hydroxyl group Available to Purchase
K Sasaki;
K Sasaki
*Laboratory of Food Hygiene, Faculty of Agriculture, Tohoku University, 1-1 Tsutsumidori-Amemiyamachi, Aoba-ku, Sendai, Japan
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M Murata;
M Murata
*Laboratory of Food Hygiene, Faculty of Agriculture, Tohoku University, 1-1 Tsutsumidori-Amemiyamachi, Aoba-ku, Sendai, Japan
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T Yasumoto;
T Yasumoto
*Laboratory of Food Hygiene, Faculty of Agriculture, Tohoku University, 1-1 Tsutsumidori-Amemiyamachi, Aoba-ku, Sendai, Japan
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G Mieskes;
G Mieskes
†Abteilung Klinische Biochemie, Zentrum für Innere Medizin, Universität Göttingen, 37070 Göttingen, Federal Republic of Germany
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A Takai
A Takai
‡Department of Physiology, School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1994 The Biochemical Society, London
1994
Biochem J (1994) 298 (2): 259–262.
Citation
K Sasaki, M Murata, T Yasumoto, G Mieskes, A Takai; Affinity of okadaic acid to type-1 and type-2A protein phosphatases is markedly reduced by oxidation of its 27-hydroxyl group. Biochem J 1 March 1994; 298 (2): 259–262. doi: https://doi.org/10.1042/bj2980259
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