A role of proton transfer in peroxidase-catalyzed process elucidated by substrates docking calculations
Open Access
- 28 August 2001
- journal article
- research article
- Published by Springer Nature in BMC Structural Biology
- Vol. 1 (1) , 3
- https://doi.org/10.1186/1472-6807-1-3
Abstract
Previous kinetic investigations of fungal-peroxidase catalyzed oxidation of N-aryl hydroxamic acids (AHAs) and N-aryl-N-hydroxy urethanes (AHUs) revealed that the rate of reaction was independent of the formal redox potential of substrates. Moreover, the oxidation rate was 3-5 orders of magnitude less than for oxidation of physiological phenol substrates, though the redox potential was similar. To explain the unexpectedly low reactivity of AHAs and AHUs we made ab initio calculations of the molecular structure of the substrates following in silico docking in the active center of the enzyme. AHAs and AHUs were docked at the distal side of heme in the sites formed by hydrophobic amino acid residues that retarded a proton transfer and finally the oxidation rate. The analogous phenol substrates were docked at different sites permitting fast proton transfer in the relay of distal His and water that helped fast substrate oxidation.Keywords
This publication has 12 references indexed in Scilit:
- Roles of Water in Heme Peroxidase and Catalase MechanismsJournal of Biological Chemistry, 2001
- N-Aryl-N-Hydroxy Urethanes as Peroxidase SubstratesMonatshefte für Chemie / Chemical Monthly, 2001
- Kinetics and thermodynamics of peroxidase- and laccase-catalyzed oxidation of N-substituted phenothiazines and phenoxazinesJBIC Journal of Biological Inorganic Chemistry, 2000
- The Structures of the Horseradish Peroxidase C-Ferulic Acid Complex and the Ternary Complex with Cyanide Suggest How Peroxidases Oxidize Small Phenolic SubstratesJournal of Biological Chemistry, 1999
- Linear free-energy relationships and inverted Marcus region in the horseradish peroxidase-catalyzed oxidation of ferrocenes by hydrogen peroxideJournal of Organometallic Chemistry, 1999
- Binding mode of benzhydroxamic acid to Arthromyces ramosus peroxidase shown by X‐ray crystallographic analysis of the complex at 1.6 Å resolutionFEBS Letters, 1997
- Factors Controlling the Substrate Specificity of Peroxidases: Kinetics and Thermodynamics of the Reaction of Horseradish Peroxidase Compound I with Phenols and Indole-3-acetic AcidsBiochemistry, 1997
- Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4Journal of Computer-Aided Molecular Design, 1996
- Crystal structure of the fungal peroxidase from Arthromyces ramosus at 1·9 Å resolutionJournal of Molecular Biology, 1994
- Kinetic and molecular orbital studies on the rate of oxidation of monosubstituted phenols and anilines by horseradish peroxidase compound IIBiochemistry, 1990