title: O2Activation in Salicylate 1,2-Dioxygenase: A QM/MM Study Reveals the Role of His162.
abstract: Nonheme iron enzymes play an important role in the aerobic degradation of aromatic ring systems. Most enzymes can only cleave substrates with electron-rich substituents, e.g., with two hydroxyl groups. However, salicylate 1,2-dioxygenase (SDO) can cleave rings with only a single hydroxyl group. We investigated the oxygen-activation mechanism of the ring fission of salicylate by SDO by computational methods using combined quantum mechanical and molecular mechanical (QM/MM) geometry optimizations, large QM calculations with 493 atoms, and QM/MM free-energy perturbations. Our results demonstrate that the reactive Fe-O2species is best described as a Fe(III)-O2•-state, which is triplet O2binding to quintet Fe(II), leading to a one-electron transfer from Fe(II) to O2. Subsequently, the O2•-group of this species attacks the aromatic ring of substrate to form an alkylperoxo intermediate. Mutation studies suggested that His162 is essential for catalysis. Our calculations indicate that His162 plays a role as an acid-base catalyst, providing a proton to the substrate.
authors: Department of Theoretical Chemistry, Lund University, Chemical Centre , P.O. Box 124, SE-221 00 Lund, Sweden.
authors: Geng
authors: G
authors: Dong
authors: Department of Theoretical Chemistry, Lund University, Chemical Centre , P.O. Box 124, SE-221 00 Lund, Sweden.
authors: Ulf
authors: U
authors: Ryde
mesh_terms: D049308:Dioxygenases / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D006639:Histidine; D049308:Dioxygenases; C511947:salicylate 1,2-dioxygenase, Pseudaminobacter salicylatoxidans; D010100:Oxygen