A role of proton transfer in peroxidase-catalyzed process elucidated by substrates docking calculations
1 Department of Enzyme Chemistry, Institute of Biochemistry, Mokslininku 12, Vilnius, 2600, Lithuania
2 Department of Biology, Faculty of Natural Sciences Vytautas Magnus University, Vileikos 8, Kaunas, 3500, Lithuania
BMC Structural Biology 2001, 1:3 doi:10.1186/1472-6807-1-3Published: 28 August 2001
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.