On the role of the axial ligand in heme proteins: a theoretical study

We present a systematic investigation of how the axial ligand in heme proteins influences the geometry, electronic structure, and spin states of the active site, and the energies of the reaction cycles. Using the density functional B3LYP method and medium-sized basis sets, we have compared models with His, His+Asp, Cys, Tyr, and Tyr+Arg as found in myoglobin and hemoglobin, peroxidases, cytochrome P450, and heme catalases, respectively. We have studied 12 reactants and intermediates of the reaction cycles of these enzymes, including complexes with H2O, OH, O2–, CH3OH, O2, H2O2, and HO2– in various formal oxidation states of the iron ion (II to V). The results show that His gives ~0.6 V higher reduction potentials than the other ligands. In particular, it is harder to reduce and protonate the O2 complex with His than with the other ligands, in accordance with the O2 carrier function of globins and the oxidative chemistry of the other proteins. For most properties, the trend Cys