Kim Na Yeon, Kim Jeong Ho, Lee Youn Ho, Lee Eun Jung, Kim Jinyoung, Lim Yoongho, Chong Youhoon, Ahn Joong-Hoon
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
J Microbiol Biotechnol. 2007 Dec;17(12):1991-5.
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.
奥密克戎甲基化是在微生物以及哺乳动物中发现的一种常见取代反应。一些奥密克戎甲基转移酶（OMTs）具有广泛的底物特异性，可用于甲基化各种化合物。来自变铅青链霉菌的DnrK编码一种蒽环类4 - 奥密克戎甲基转移酶，它以洋红霉素为底物，其晶体结构已被确定。使用各种黄酮类化合物对DnrK进行了成功的分子对接实验，预测一些黄酮类化合物如芹菜素和染料木黄酮可作为底物。基于这些结果，成功地用DnrK对各种黄酮类化合物进行了奥密克戎甲基化。甲基化位置确定在C7的羟基处。使用定点诱变可以鉴定出DnrK与芹菜素酶促反应的重要氨基酸残基。分子对接可能有助于预测其他OMTs的底物特异性范围。
