title: Why does the enzyme SyrB2 chlorinate, but does not hydroxylate, saturated hydrocarbons? A density functional theory (DFT) study.
abstract: Syringomycin halogenase (SyrB2) is a non-heme Fe(II)/alpha-ketoglutarate (alphaKG)-dependent enzyme which catalyses halogenation of saturated hydrocarbons, but unlike other closely related enzymes, does not catalyse the corresponding hydroxylation reaction. We have carried out density functional theory (DFT) calculations to try to understand this specificity. Calculations which include only the basic six coordinate iron centre suggest that both hydroxylation and halogenation are feasible by a rebound mechanism. We suggest that the hydroxylation reaction is inhibited by protonation of the hydroxo intermediate, leading to only chlorination. We propose that this hypothesis could be tested using a mutant enzyme.
authors.affiliation: School of Chemistry, University of Manchester, Oxford Road, Manchester, UKM13 9PL.
authors.forename: Shanthi
authors.initials: S
authors.lastname: Pandian
authors.forename: Mark A
authors.initials: MA
authors.lastname: Vincent
authors.forename: Ian H
authors.initials: IH
authors.lastname: Hillier
authors.forename: Neil A
authors.initials: NA
authors.lastname: Burton
mesh_terms: D055162:Biocatalysis; D003198:Computer Simulation; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D008968:Molecular Conformation; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D006843:Hydrocarbons, Chlorinated; D007658:Ketone Oxidoreductases; C023096:2-oxoglutarate synthase