Beyond active site residues: overall structural dynamics control catalysis in flavin-containing and heme-containing monooxygenases
| Autor: | Marco W. Fraaije, Maximilian J. L. J. Fürst, Filippo Fiorentini |
|---|---|
| Přispěvatelé: | Biotechnology |
| Jazyk: | angličtina |
| Předmět: |
MECHANISM
Conformational change DIRECTED EVOLUTION Molecular Conformation OXYGEN ACTIVATION Flavin group Heme Molecular Dynamics Simulation CONFORMATIONAL-CHANGE Cofactor C4A-HYDROPEROXYFLAVIN Mixed Function Oxygenases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology Catalytic Domain Flavins CRYSTAL-STRUCTURE Amino Acids PLASTICITY Molecular Biology MOBILE FLAVIN 030304 developmental biology 0303 health sciences biology Molecular Structure Chemistry Active site Cytochrome P450 Monooxygenase Directed evolution Molecular Docking Simulation HYDROXYLASE biology.protein Biophysics ALLOSTERY 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Current Opinion in Structural Biology Current Opinion in Structural Biology, 59, 29-37 |
| ISSN: | 0959-440X |
| DOI: | 10.1016/j.sbi.2019.01.019 |
| Popis: | Monooxygenases (MOs) face the challenging reaction of an organic target, oxygen and a cofactor – most commonly heme or flavin. To correctly choreograph the substrates spatially and temporally, MOs evolved a variety of strategies, which involve structural flexibility. Besides classical domain and loop movements, flavin-containing MOs feature conformational changes of their flavin prosthetic group and their nicotinamide cofactor. With similar mechanisms emerging in various subclasses, their generality and involvement in selectivity are intriguing questions. Cytochrome P450 MOs are often inherently plastic and large movements of individual segments throughout the entire structure occur. As these complicated and often unpredictable movements are largely responsible for substrate uptake, engineering strategies for these enzymes were mostly successful when randomly mutating residues across the entire structure. |
| Databáze: | OpenAIRE |
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