title: Electronic structure analysis of the oxygen-activation mechanism by Fe(II)- and α-ketoglutarate (αKG)-dependent dioxygenases.
abstract: α-Ketoglutarate (αKG)-dependent nonheme iron enzymes utilize a high-spin (HS) ferrous center to couple the activation of oxygen to the decarboxylation of the cosubstrate αKG to yield succinate and CO(2), and to generate a high-valent ferryl species that then acts as an oxidant to functionalize the target C-H bond. Herein a detailed analysis of the electronic-structure changes that occur in the oxygen activation by this enzyme was performed. The rate-limiting step, which is identical on the septet and quintet surfaces, is the nucleophilic attack of the distal O atom of the O(2) adduct on the carbonyl group in αKG through a bicyclic transition state ((5, 7) TS1). Due to the different electronic structures in (5, 7) TS1, the decay of (7)TS1 leads to a ferric oxyl species, which undergoes a rapid intersystem crossing to form the ferryl intermediate. By contrast, a HS ferrous center ligated by a peroxosuccinate is obtained on the quintet surface following (5)TS1. Thus, additional two single-electron transfer steps are required to afford the same Fe(IV)-oxo species. However, the triplet reaction channel is catalytically irrelevant. The biological role of αKG played in the oxygen-activation reaction is dual. The αKG LUMO (C=O π*) serves as an electron acceptor for the nucleophilic attack of the superoxide monoanion. On the other hand, the αKG HOMO (C1-C2 σ) provides the second and third electrons for the further reduction of the superoxide. In addition to density functional theory, high-level ab initio calculations have been used to calculate the accurate energies of the critical points on the alternative potential-energy surfaces. Overall, the results delivered by the ab initio calculations are largely parallel to those obtained with the B3LYP density functional, thus lending credence to our conclusions.
authors.affiliation: Max-Plank Institute for Bioinorganic Chemistry, Stiftstrasse 34-36, 45470 Mülheim an der Ruhr, Germany.
authors.forename: Shengfa
authors.initials: S
authors.lastname: Ye
authors.forename: Christoph
authors.initials: C
authors.lastname: Riplinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Hansen
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bollinger
authors.forename: Frank
authors.initials: F
authors.lastname: Neese
mesh_terms: D002384:Catalysis; D049308:Dioxygenases / Q000378:metabolism*; D005296:Ferrous Compounds / Q000737:chemistry*; D007656:Ketoglutaric Acids / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*
chemical_list: D005296:Ferrous Compounds; D007656:Ketoglutaric Acids; D049308:Dioxygenases; D010100:Oxygen