Siegrist Jutta, Netzer Julia, Mordhorst Silja, Karst Lukas, Gerhardt Stefan, Einsle Oliver, Richter Michael, Andexer Jennifer N
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Germany.
Institute of Biochemistry, Albert-Ludwigs-University Freiburg, Germany.
FEBS Lett. 2017 Jan;591(2):312-321. doi: 10.1002/1873-3468.12530. Epub 2017 Jan 8.
Mg -dependent catechol-O-methyltransferases occur in animals as well as in bacteria, fungi and plants, often with a pronounced selectivity towards one of the substrate's hydroxyl groups. Here, we show that the bacterial MxSafC exhibits excellent regioselectivity for para as well as for meta methylation, depending on the substrate's characteristics. The crystal structure of MxSafC was solved in apo and in holo form. The structure complexed with a full set of substrates clearly illustrates the plasticity of the active site region. The awareness that a wide range of factors influences the regioselectivity will aid the further development of catechol-O-methyltransferases as well as other methyltransferases as selective and efficient biocatalysts for chemical synthesis.
依赖镁的儿茶酚-O-甲基转移酶存在于动物以及细菌、真菌和植物中，通常对底物的一个羟基具有明显的选择性。在此，我们表明，细菌MxSafC根据底物的特性，对间位和对位甲基化均表现出优异的区域选择性。已解析出MxSafC的无辅基形式和全酶形式的晶体结构。与全套底物复合的结构清楚地说明了活性位点区域的可塑性。认识到多种因素会影响区域选择性，将有助于儿茶酚-O-甲基转移酶以及其他甲基转移酶作为化学合成中选择性高效生物催化剂的进一步发展。
