Cytochrome P450BM-3 reduces aldehydes to alcohols through a direct hydride transfer
| Autor: | Rüdiger Kaspera, Rheem A. Totah, Tariku Sahele, Kyle Lakatos |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cytochrome
Stereochemistry Biophysics Reductase Photochemistry Biochemistry Aldehyde Redox Benzaldehyde chemistry.chemical_compound Bacterial Proteins Cytochrome P-450 Enzyme System Imidazole Moiety Molecular Biology NADPH-Ferrihemoprotein Reductase chemistry.chemical_classification Aldehydes biology Hydride Cell Biology Kinetics chemistry Alcohols biology.protein Oxidation-Reduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 418:464-468 |
| ISSN: | 0006-291X |
| Popis: | Highlights: Black-Right-Pointing-Pointer Cytochrome P450BM-3 reduced aldehydes to alcohols efficiently (k{sub cat} {approx} 25 min{sup -1}). Black-Right-Pointing-Pointer Reduction is a direct hydride transfer from R-NADP{sup 2}H to the carbonyl moiety. Black-Right-Pointing-Pointer P450 domain variants enhance reduction through potential allosteric/redox interactions. Black-Right-Pointing-Pointer Novel reaction will have implications for metabolism of xenobiotics. -- Abstract: Cytochrome P450BM-3 catalyzed the reduction of lipophilic aldehydes to alcohols efficiently. A k{sub cat} of {approx}25 min{sup -1} was obtained for the reduction of methoxy benzaldehyde with wild type P450BM-3 protein which was higher than in the isolated reductase domain (BMR) alone and increased in specific P450-domain variants. The reduction was caused by a direct hydride transfer from preferentially R-NADP{sup 2}H to the carbonyl moiety of the substrate. Weak substrate-P450-binding of the aldehyde, turnover with the reductase domain alone, a deuterium incorporation in the product from NADP{sup 2}H but not D{sub 2}O, and no inhibition by imidazole suggests the reductase domain of P450BM-3 as the potential catalytic site. However, increased aldehyde reduction by P450 domain variants (P450BM-3 F87A T268A) may involve allosteric or redox mechanistic interactions between heme and reductase domains. This is a novel reduction of aldehydes by P450BM-3 involving a direct hydride transfer and could have implicationsmore » for the metabolism of endogenous substrates or xenobiotics.« less |
| Databáze: | OpenAIRE |
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