The proximal hydrogen-bonded residue controls the stability of the compound II intermediate of peroxidases and catalases

The structural and energetic properties of the compound II intermediate in the catalytic reaction of peroxidases and catalases are compared in order to investigate why catalases, unlike peroxidases, rarely form compound II. Our calculations, based on the density functional theory (DFT)/Car - Parrinello molecular dynamics methodology (CPMD), show that catalase compound II is a stable intermediate with respect to ligand dissociation, with Fe - ligand binding energies comparable to those found for other hemeproteins such as myoglobin and cytochrome c. Nevertheless, catalase shows much weaker iron - ligand bonds compared to those of peroxidase, which is due to the opposite effect of the proximal hydrogen-bonded residues (Arg+ in catalase and Asp- in peroxidase). Comparison with the available structural information suggests that, contrary to the often assumed oxoferryl bond of compound II, some of the reported structures might instead correspond to a hydroxyferryl bond. Some hints on the role of the proximal hydrogen-bonded residues in modulating the stability of the different species during the catalytic reaction are provided.This work was supported by the CIRIT under project 2001SGR-00044. The computer resources were provided by the CEPBA-IBM Research Institute of Barcelona. C.R. thanks the financial support from the Ramon y Cajal program of the “Ministerio de Ciencia y Tecnología” (MCYT)Peer Reviewe