A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase
| Autor: | Nobufusa Serizawa, Tatsuji Matsuoka |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Cytochrome
Stereochemistry 25-Hydroxyvitamin D3 1-alpha-hydroxylase Biophysics Naphthalenes Reductase Biology Hydroxylation Models Biological Biochemistry Mixed Function Oxygenases chemistry.chemical_compound Endocrinology Cytochrome P-450 Enzyme System Cytochrome C1 Enzyme Stability NADH NADPH Oxidoreductases Lovastatin Pravastatin Flavoproteins Nucleotides Cytochrome c Cytochrome P450 reductase Streptomyces chemistry Heptanoic Acids Coenzyme Q – cytochrome c reductase Oxygenases biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1084:35-40 |
| ISSN: | 0005-2760 |
| DOI: | 10.1016/0005-2760(91)90052-j |
| Popis: | Pravastatin (CS-514) is a tissue selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), a key enzyme in cholesterol biosysthesis. This compound is obtained by hydroxylation of ML-236B (mevastatin) in Streptomyces carbophilus catalyzed by a cytochrome P -450 sca monooxygenase system. NADH-cytochrome P -450 redactase was purified to homogeneity from S. carbophilus as a single polypeptide chain with a molecular weight of 51 kDa, and reconstituted the hydroxylation in vitro with cytochrome P -450 sca , NADH and O 2 . This protein contained FAD and FMN molecule. The FMN molecule was easily dissociated from the reductase, and had a K d value of 5·10 −5 M. The cytochrome P -450 sca monooxygenase system was present in the soluble fraction and consisted of only two components, cytochrome P -450 sca and flavoprotein. Our results constitute the demonstration of a two component-type cytochrome P -450 system in a prokaryote. |
| Databáze: | OpenAIRE |
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