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O-Methylation of flavonoids using DnrK based on molecular docking
Na Yeon Kim1, Jeong Ho Kim, Youn Ho Lee
1Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Journal of Microbiology and Biotechnology
|January 3, 2008
Summary
Omicron-methyltransferases (OMTs) can modify diverse compounds. Researchers found that DnrK, an OMT, successfully methylated flavonoids like apigenin at the C7 hydroxyl group, identifying key amino acids involved.
Area of Science:
- Biochemistry
- Enzymology
- Microbiology
Background:
- Omicron-methylation is a prevalent substitution reaction in both microbial and mammalian systems.
- Omicron-methyltransferases (OMTs) exhibit broad substrate specificity, enabling the modification of various compounds.
- DnrK, an anthracycline 4-Omicron-methyltransferase from Streptomyces peucetius, utilizes carminomycin as a substrate and its structure is known.
Purpose of the Study:
- To investigate the potential of DnrK to methylate flavonoids.
- To determine the specific site of methylation on flavonoids by DnrK.
- To identify key amino acid residues in DnrK responsible for flavonoid methylation.
Main Methods:
- Molecular docking simulations were performed using DnrK and various flavonoid compounds.
- In vitro Omicron-methylation reactions were conducted using DnrK with predicted flavonoid substrates.
- Site-directed mutagenesis was employed to identify critical amino acid residues for enzymatic activity.
Main Results:
- Molecular docking successfully predicted apigenin and genistein as potential substrates for DnrK.
- DnrK effectively catalyzed the Omicron-methylation of various flavonoids, with methylation occurring at the C7 hydroxyl group.
- Specific amino acid residues essential for DnrK's enzymatic activity with apigenin were identified through mutagenesis.
Conclusions:
- DnrK demonstrates the capability to methylate flavonoids at the C7 hydroxyl group.
- Site-directed mutagenesis revealed crucial amino acid residues involved in DnrK-mediated flavonoid methylation.
- Molecular docking serves as a valuable tool for predicting the substrate specificity of OMTs.
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