Catalases are ubiquitous enzymes that prevent cell oxidative damage by degrading hydrogen peroxide to water and oxygen (2H2O2 → 2H2O + O2) with high efficiency. The enzyme is first oxidized to a high-valent iron intermediate, known as Compound I (Cpd I, Por+-FeIV=O) which, at difference from other hydroperoxidases, is reduced back to the resting state by further reacting with H2O2. The normal catalase activity is reduced if Cpd I is consumed in a competing side reaction, forming a species named Cpd I. In recent years, Density Functional Theory (DFT) methods have unraveled the electronic configuration of these high-valent iron species, helping to assign the intermediates trapped in the crystal structures of oxidized catalases. It has been demonstrated that the a priori assumption that the H+/H - type of mechanism for Cpd I reduction leads to the generation of singlet oxygen is not justified. Moreover, it has been shown by ab initio metadynamics simulations that two pathways are operative for Cpd I reduction: a His-mediated mechanism (described as H·/H+ + e-) in which the distal His acts as an acid-base catalyst and a direct mechanism (described as H·/H·) in which the distal His does not play a direct role. Independently of the mechanism, the reaction proceeds by two one-electron transfers rather than one two-electron transfer, as previously assumed. Electron transfer to Cpd I, regardless of whether the electron is exogenous or endogenous, facilitates protonation of the oxoferryl group, to the point that formation of Cpd I may be controlled by the easiness of protonation of reduced Cpd I. © 2012 Elsevier Inc. All rights reserved.
|Journal||Archives of Biochemistry and Biophysics|
|Publication status||Published - 15 Sep 2012|
- Ab initio molecular dynamics
- Density Functional Theory
- Enzyme catalysis