Specificity and mechanism of carbohydrate demethylation by cytochrome P450 monooxygenases
| Autor: | Craig S. Robb, Jan-Hendrik Hehemann, Uwe T. Bornscheuer, Lukas Reisky |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Subfamily Crystallography X-Ray Biochemistry Substrate Specificity 03 medical and health sciences Bacterial Proteins Cytochrome P-450 Enzyme System Protein Domains Oxidoreductase Catalytic Domain carbohydrate metabolism Amino Acid Sequence crystallography Molecular Biology Research Articles Demethylation chemistry.chemical_classification Binding Sites biology Chemistry Cytochrome P450 Active site Cell Biology Monooxygenase 030104 developmental biology Enzyme Structural biology cytochrome p450 ddc:540 biology.protein Mutagenesis Site-Directed carbohydrate-active enzyme O-demethylase Sugars Flavobacteriaceae Research Article Protein Binding |
| Zdroj: | Biochemical Journal The biochemical journal / Reviews 475(23), 3875-3886 (2018). doi:10.1042/BCJ20180762 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | The biochemical journal / Reviews 475(23), 3875 - 3886 (2018). doi:10.1042/BCJ20180762 Degradation of carbohydrates by bacteria represents a key step in energy metabolism that can be inhibited by methylated sugars. Removal of methyl groups, which is critical for further processing, poses a biocatalytic challenge because enzymes need to overcome a high energy barrier. Our structural and computational analysis revealed how a member of the cytochrome P450 family evolved to oxidize a carbohydrate ligand. Using structural biology, we ascertained the molecular determinants of substrate specificity and revealed a highly specialized active site complementary to the substrate chemistry. Invariance of the residues involved in substrate recognition across the subfamily suggests that they are critical for enzyme function and when mutated, the enzyme lost substrate recognition. The structure of a carbohydrate-active P450 adds mechanistic insight into monooxygenase action on a methylated monosaccharide and reveals the broad conservation of the active site machinery across the subfamily. Published by Portland Pr., London [u.a.] |
| Databáze: | OpenAIRE |
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