New Proluciferin Substrates for Human CYP4 Family Enzymes
| Autor: | Gerhard Wolber, Jingyao Liu, Matthias Bureik, Erik J. Sorensen, David Machalz |
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| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
chemistry.chemical_classification biology 010405 organic chemistry Stereochemistry Cytochrome P450 Bioengineering Substrate recognition General Medicine Metabolism 01 natural sciences Applied Microbiology and Biotechnology Biochemistry 0104 chemical sciences CYP4 Family Enzyme Biotransformation chemistry Docking (molecular) 010608 biotechnology biology.protein Homology modeling Molecular Biology Biotechnology |
| Zdroj: | Applied Biochemistry and Biotechnology. 193:218-237 |
| ISSN: | 1559-0291 0273-2289 |
| Popis: | We report the synthesis of seven new proluciferins for convenient activity determination of enzymes belonging to the cytochrome P450 (CYP) 4 family. Biotransformation of these probe substrates was monitored using each of the twelve human CYP4 family members, and eight were found to act at least on one of them. For all substrates, activity of CYP4Z1 was always highest, while that of CYP4F8 was always second highest. Site of metabolism (SOM) predictions involving SMARTCyp and docking experiments helped to rationalize the observed activity trends linked to substrate accessibility and reactivity. We further report the first homology model of CYP4F8 including suggested substrate recognition residues in a catalytically competent conformation accessed by replica exchange solute tempering (REST) simulations. |
| Databáze: | OpenAIRE |
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