Differences between the structural requirements for ABA 8″-hydroxylase inhibition and for ABA activity
| Autor: | Kanzo Sakata, Nobuhiro Hirai, Shigeki Saito, Yoshiharu Araki, Masaharu Mizutani, Kotomi Ueno, Yasushi Todoroki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Protein Conformation
Clinical Biochemistry Arabidopsis Pharmaceutical Science Germination Hydroxylation Biochemistry Mixed Function Oxygenases Substrate Specificity chemistry.chemical_compound Non-competitive inhibition Cytochrome P-450 Enzyme System Plant Growth Regulators Microsomes Drug Discovery Enzyme Inhibitors Molecular Biology Abscisic acid Plant Proteins chemistry.chemical_classification Unspecific monooxygenase biology Chemistry organic chemicals fungi Organic Chemistry food and beverages Cytochrome P450 Oryza Monooxygenase Lettuce biology.organism_classification Enzyme Activation Kinetics Enzyme Enzyme inhibitor Seedlings biology.protein Molecular Medicine Plant hormone Abscisic Acid |
| Zdroj: | Bioorganic & Medicinal Chemistry. 13(10):3359-3370 |
| ISSN: | 0968-0896 |
| Popis: | A major catabolic enzyme of the plant hormone abscisic acid (ABA) is the cytochrome P450 monooxygenase ABA 8′-hydroxylase. For designing a specific inhibitor of this enzyme, the substrate specificity and inhibition of CYP707A3, an ABA 8′-hydroxylase from Arabidopsis thaliana , was investigated using 45 structural analogues of ABA and compared to the structural requirements for ABA activity. Substrate recognition by the enzyme strictly required the 6′-methyl groups (C-8′ and C-9′), which were unnecessary for ABA activity, whereas elimination of the 3-methyl (C-6) and 1′-hydroxyl groups, which significantly affected ABA activity, had little effect on the ability of analogues to competitively inhibit the enzyme. Fluorination at C-8′ and C-9′ resulted in resistance to 8′-hydroxylation and competitive inhibition of the enzyme. In particular, 8′,8′-difluoro-ABA and 9′,9′-difluoro-ABA yielded no enzyme reaction products and strongly inhibited the enzyme ( K I = 0.16 and 0.25 μM, respectively). |
| Databáze: | OpenAIRE |
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