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

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On the role of the axial ligand in heme proteins: a theoretical study. / Rydberg, Patrik; Sigfridsson, Emma; Ryde, Ulf.

In: Journal of Biological Inorganic Chemistry, Vol. 9, No. 2, 2004, p. 203-223.

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T1 - On the role of the axial ligand in heme proteins: a theoretical study

AU - Rydberg, Patrik

AU - Sigfridsson, Emma

AU - Ryde, Ulf

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)

PY - 2004

Y1 - 2004

N2 - 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, O-2, H2O2, and HO2- in various formal oxidation states of the iron ion (II to V). The results show that His gives similar to0.6 V higher reduction potentials than the other ligands. In particular, it is harder to reduce and protonate the O-2 complex with His than with the other ligands, in accordance with the O-2 carrier function of globins and the oxidative chemistry of the other proteins. For most properties, the trend Cys<Tyr<Tyr+Arg<His+Asp<His is found, reflecting the donor capacity of the various ligands. Thus, it is easier to reduce compound I with a His+Asp ligand than with a Cys ligand, in accordance with the one-electron chemistry of peroxidases and the hydroxylation reactions of cytochromes P450. However, the Tyr complexes have an unusually low affinity for all neutral ligands, giving them a slightly enhanced driving force in the oxidation of H2O2 by compound I.

AB - 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, O-2, H2O2, and HO2- in various formal oxidation states of the iron ion (II to V). The results show that His gives similar to0.6 V higher reduction potentials than the other ligands. In particular, it is harder to reduce and protonate the O-2 complex with His than with the other ligands, in accordance with the O-2 carrier function of globins and the oxidative chemistry of the other proteins. For most properties, the trend Cys<Tyr<Tyr+Arg<His+Asp<His is found, reflecting the donor capacity of the various ligands. Thus, it is easier to reduce compound I with a His+Asp ligand than with a Cys ligand, in accordance with the one-electron chemistry of peroxidases and the hydroxylation reactions of cytochromes P450. However, the Tyr complexes have an unusually low affinity for all neutral ligands, giving them a slightly enhanced driving force in the oxidation of H2O2 by compound I.

U2 - 10.1007/s00775-003-0515-y

DO - 10.1007/s00775-003-0515-y

M3 - Article

C2 - 14727167

VL - 9

SP - 203

EP - 223

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 1432-1327

IS - 2

ER -