title: Functional and structural characterisation of a bacterial O-methyltransferase and factors determining regioselectivity.
abstract: Mg2+-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.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Siegrist
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Netzer
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Silja
authors.initials: S
authors.lastname: Mordhorst
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Karst
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerhardt
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-University Freiburg, Germany.|BIOSS Centre for Biological Signalling Studies, Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Einsle
authors.affiliation: Bio-, Electro- and Chemocatalysis BioCat, Straubing Branch, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Straubing, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Richter
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Germany.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Andexer
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D002394:Catechol O-Methyltransferase / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008958:Models, Molecular; D016940:Myxococcus / Q000201:enzymology*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D002394:Catechol O-Methyltransferase
keywords: SafC; biocatalysis; catechol; catechol-O-methyltransferase; methylation; structure-function relationship