Novel inhibitors of Nocardia erythropolis cholesterol oxidase: Screening and characterization
| Autor: | Bernard Witholt, Paul G. M. Hesselink, Antonius Kerkenaar |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
chemistry.chemical_classification
Fenpropimorph biology Cholesterol oxidase Stereochemistry Health Toxicology and Mutagenesis Active site General Medicine biology.organism_classification chemistry.chemical_compound Enzyme chemistry Enzyme inhibitor Morpholine biology.protein Actinomycetales Agronomy and Crop Science Isomerization |
| Zdroj: | Pesticide biochemistry and physiology, 33(1), 69-77 |
| ISSN: | 0048-3575 |
| DOI: | 10.1016/0048-3575(89)90077-1 |
| Popis: | Nocardia erythropolis cholesterol oxidase catalyzes two distinct reactions: the oxidation of a 3-hydroxy-Δ5-steroid to a 3-keto-Δ5-derivative followed by the isomerization to a 3-keto-Δ4-steroid. As this enzyme has potential applications in steroid hormone synthesis, separation of these activities would be useful. In this study, we were able to demonstrate that fenpropimorph and tridemorph were effective inhibitors of cholesterol oxidase from N. erythropolis in vitro. The isomerization reaction was the most probable target of a reversible inhibition mechanism. Tridemorph probably blocked the active site, thus lowering the apparent enzyme concentration. Fenpropimorph acted via an unknown mechanism. A tertiary nitrogen atom able to form a morpholinium ion and the two morpholine methyl groups, preferably in cis configuration, were found to be essential for inhibition. The three dimethylmorpholine side chains tested were found to be interchangeable and replacement of the oxygen atom by carbon was without any major effect. These findings suggest an inhibition mechanism in which the positively charged morpholinium ion interacts strongly with an aspartate residue in the catalytic center of the enzyme, the inhibitor molecule being correctly oriented in the active site due to its resemblance to cholesterol. |
| Databáze: | OpenAIRE |
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