10.1021/ja1110706.s001
M. Alfonso-Prieto
M.
Alfonso-Prieto
H. Oberhofer
H.
Oberhofer
M. L. Klein
M. L.
Klein
C. Rovira
C.
Rovira
J. Blumberger
J.
Blumberger
Proton Transfer Drives Protein Radical Formation in Helicobacter pylori Catalase but Not in Penicillium vitale Catalase
American Chemical Society
2011
hydrogen peroxide
Helicobacter pylori catalase
factor
Penicillium vitale catalase
Proton Transfer Drives Protein Radical Formation
Cpd
Penicillium vitale CatalaseHeme catalases
catalase activity
electron transfer reaction
migration
Helicobacter pylori Catalase
HPC
ferryl oxygen atom
2011-03-30 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Proton_Transfer_Drives_Protein_Radical_Formation_in_Helicobacter_pylori_Catalase_but_Not_in_Penicillium_vitale_Catalase/2675551
Heme catalases prevent cells from oxidative damage by decomposing hydrogen peroxide into water and molecular oxygen. Here we investigate the factors that give rise to an undesirable side reaction competing with normal catalase activity, the migration of a radical from the heme active site to the protein in the principal reaction intermediate compound I (Cpd I). Recently, it has been proposed that this electron transfer reaction takes place in Cpd I of Helicobacter pylori catalase (HPC), but not in Cpd I of Penicillium vitale catalase (PVC), where the oxidation equivalent remains located on the heme active site. Unraveling the factors determining the different radical locations could help engineer enzymes with enhanced catalase activity for detection or removal of hydrogen peroxide. Using quantum mechanics/molecular mechanics metadynamics simulations, we show that radical migration in HPC is facilitated by the large driving force (−0.65 eV) of the subsequent proton transfer from a histidine residue to the ferryl oxygen atom of reduced Cpd I. The corresponding free energy in PVC is significantly smaller (−0.19 eV) and, as we argue, not sufficiently high to support radical migration. Our results suggest that the energetics of oxoferryl protonation is a key factor regulating radical migration in catalases and possibly also in hydroperoxidases.