QM/MM studies of the electronic structure of the compound I intermediate in cytochrome c peroxidase and ascorbate peroxidase
- 13 September 2005
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Dalton Transactions
- No. 21,p. 3470-3476
- https://doi.org/10.1039/b505407a
Abstract
Cytochrome c peroxidase (CcP) and ascorbate peroxidase (APX) both involve reactive haem oxoferryl intermediates known as ‘compound I’ species. These two enzymes also have a very similar structure, especially in the vicinity of the haem group. Despite this similarity, the electronic structure of compound I in the two enzymes is known to be very different. Compound I intermediates have three unpaired electrons, two of which are always situated on the Fe–O core, whilst the third is located in a porphyrin orbital in APX and many other compound I species. In CcP, however, this third unpaired electron is positioned on a tryptophan residue lying close to the haem ring. The same residue is present in the same position in APX, yet it is not oxidized in that case. We report QM/MM calculations, using accurate B3LYP density functional theory for the QM region, on the active intermediate for both enzymes. We reproduce the observed difference in electronic structure, and show that it arises as a result of subtle electrostatic effects which affect the ionization potential of both the tryptophan and porphyrin groups. The computed structures of both enzymes do not involve deprotonation of the tryptophan group, or protonation of the oxoferryl oxygen.Keywords
This publication has 59 references indexed in Scilit:
- Hydrogenases: active site puzzles and progressCurrent Opinion in Chemical Biology, 2004
- Aromatic Hydroxylation by Cytochrome P450: Model Calculations of Mechanism and Substituent EffectsJournal of the American Chemical Society, 2003
- Crystal structure of the ascorbate peroxidase–ascorbate complexNature Structural & Molecular Biology, 2003
- All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of ProteinsThe Journal of Physical Chemistry B, 1998
- Electrostatic modulation of electron transfer in the active site of heme peroxidasesJBIC Journal of Biological Inorganic Chemistry, 1997
- Heme-Containing OxygenasesChemical Reviews, 1996
- Solvent effects on protein motion and protein effects on solvent motionJournal of Molecular Biology, 1989
- Deformable stochastic boundaries in molecular dynamicsThe Journal of Chemical Physics, 1983
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983
- Theoretical studies of enzymic reactions: Dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozymeJournal of Molecular Biology, 1976