Deuterium isotope effect on enantioselectivity in the Comamonas testosteroni quinohemoprotein alcohol dehydrogenase-catalyzed kinetic resolution of rac-2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, solketal
| Autor: | Jaap A. Jongejan, Wilfred R. Hagen, Aldo Jongejan |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Stereochemistry
PQQ Cofactor Biophysics Quinolones Biochemistry Catalysis Analytical Chemistry Kinetic resolution chemistry.chemical_compound Bacterial Proteins Kinetic isotope effect Solketal Hydroxymethyl Comamonas testosteroni Molecular Biology Comamonas Ethanol biology Quinones Dioxolanes Stereoisomerism Deuterium biology.organism_classification Alcohol Oxidoreductases Kinetics chemistry Dioxolane Enantiomer |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1647:297-302 |
| ISSN: | 1570-9639 |
| Popis: | Isotopic substitution provides an effective tool to probe the mechanism of enzyme-catalyzed reactions. To our knowledge, kinetic isotope effects on the enantioselectivity of enzymes have not been reported. We investigated the effect of deuterium substitution on the enantiomeric ratio, E, of PQQ-containing quinohemoprotein alcohol dehydrogenase, QH-ADH, from Comamonas testosteroni in the ferricyanide-coupled kinetic resolution of rac-2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, solketal. Under otherwise identical conditions, we measured E=30 for solketal and E=6 for rac-2,2-dimethyl-4-[1,1-2H]hydroxymethyl-1,3-[5,5,4-2H]dioxolane, d(5)-solketal. It is proposed that isotopic substitution affects the relative kinetic weights of the initial hydron/deuteron transfer from substrate to cofactor and the subsequent proton/deuteron shift in the cofactor-product complex. The latter step becomes more important in the deuterated complex to the extent that the enantiomer discrimination in the first step is partially overruled. |
| Databáze: | OpenAIRE |
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