O-Methylation of flavonoids using DnrK based on molecular docking.
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.
Kim
Na Yeon
NY
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Kim
Jeong Ho
JH
Lee
Youn Ho
YH
Lee
Eun Jung
EJ
Kim
Jinyoung
J
Lim
Yoongho
Y
Chong
Youhoon
Y
Ahn
Joong-Hoon
JH
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
D004269:DNA, Bacterial; D005419:Flavonoids; C492547:DnrK protein, Streptomyces peucetius; D008780:Methyltransferases