title: O-Methylation of flavonoids using DnrK based on molecular docking.
abstract: Omicron-Methylation is a common substitution reaction found in microbes as well as in mammalians. Some of the Omicron-methyltransferases (OMTs) have broad substrate specificity and could be used to methylate various compounds. DnrK from Streptomyces peucetius encodes an anthracycline 4-Omicron-methyltransferase, which uses carminomycin as a substrate, and its crystal structure has been determined. Molecular docking experiments with DnrK using various flavonoids were successfully conducted, and some of the flavonoids such as apigenin and genistein were predicted to serve as substrates. Based on these results, Omicron-methylations of various flavonoids with the DnrK were successfully carried out. The methylation position was determined to be at the hydroxyl group of C7. Important amino acid residues for the enzymatic reaction of DnrK with apigenin could be identified using site-directed mutagenesis. Molecular docking could be useful to predict the substrate specificity ranges of other OMTs.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors.forename: Na Yeon
authors.initials: NY
authors.lastname: Kim
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Youn Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.forename: Youhoon
authors.initials: Y
authors.lastname: Chong
authors.forename: Joong-Hoon
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005419:Flavonoids / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship
chemical_list: D004269:DNA, Bacterial; D005419:Flavonoids; C492547:DnrK protein, Streptomyces peucetius; D008780:Methyltransferases