Proximal ligand effects on electronic structure and spectra of compound I of peroxidases

Abstract

ABSTRACT:Computational studies exploring the extent to which differences in proximal axial ligands modulate structure, spectra, and function of peroxidases have been performed. To this end, three heme models of compound I were characterized differing only in the axial ligand. The axial ligands considered were L=ImH, Im À , that are alternative protonation models for a typical peroxidase with an imidazole ligand such as horseradish peroxidase (HRP-I), and L=SCH-that is a model for an unsual peroxidase, chloroperoxidase (CPO-I). Density functional calculations (DFTs) were performed to determine the optimized geometries and electronic structure of each of these three species. Their electronic spectra were also calculated at the DFT optimized geometries, using the INDO/S/CI method. The results of these studies led to the following conclusions: (1) the presence of the nearby Asp in a typical peroxidase does indeed decrease the energy required to deprotonate the imidazole making the two forms essentially degenerate, (2) neither the state of protonation of the imidazole ligand nor the change in axial ligand from an imidazole in typical peroxidases such as HRP to a mercaptide in CPO significantly alters the characteristics of the lowest energy spin state or the electronic structure of compound I in a way that can obviously affect function, (3) both the Im À and ImH forms of the peroxidase compound I (HRP-I) lead to the same dramatic reduction in intensity relative to the ferric resting form observed experimentally. However, only in the ImH form of HRP-I does the calculated relative shift of one component of the Soret bands relative to CPO-I agree with that observed in the transient spectra of HRP-I compared to CPO-I. These results taken together strongly indicate that factors other than the nature of the proximal axial ligand are the main determinants of function.

Crystal structure of the pristine peroxidase ferryl center and its relevance to proton-coupled electron transfer

“…In both cases, protein charges were assigned using the Amber ff99SB force field. Heme parameters, including the oxyferryl oxygen atom, were taken from density functional calculations by Harris and Loew (39). The first method used the H++ webserver (biophysics.cs.vt.…”

High-valent transition metal centers and noninnocent ligands in metalloporphyrins and related molecules: a broad overview based on quantum chemical calculations

“…It is certainly possible that the intriguing electronic dierences among the dierent compound I species described above are relatively unimportant, from the point of view of differences in reactivity among the dierent enzymes. Harris and Loew [48] have shown that dierences involving the proximal ligand result in minimal dierences in the charge distribution, spin density pro®le, and bond order of the ferryl group. For example, for the ferryl groups in a variety of compound I model compounds, the Fe and O spin populations are always almost exactly 1:1, assuming ferromagnetic coupling between the ferryl group and the radical.…”

How axial ligands control the reactivity of high-valent iron(IV)–oxo porphyrin π-cation radicals in alkane hydroxylation: A computational study

“…Thus, the experimental evidence discussed above demonstrates unambiguously that there are remarkable axial ligand effects on the reactivities of high-valent iron(IV)-oxo complexes of heme and nonheme ligands in oxygenation reactions. In this communication, we have investigated the hydroxylation of cyclohexane by highvalent iron(IV)-oxo porphyrin p-cation radicals bearing different anionic axial ligands, to gain a better understanding of the role of axial ligands in controlling the reactivity of iron(IV)-oxo intermediates from a theoretical viewpoint [7,[14][15][16][17].…”