Coupling between oxidation state and hydrogen bond conformation in heme proteins

Abstract

In all heme proteins for which crystal structures are available, the NE of a histidyl residue is bonded to the heme iron and Na is hydrogen bonded to a carbonyl oxygen of the peptide backbone. We investigate here the possibility that a change in oxidation state of the iron or a change in the geometry of this hydrogen bond might change the hydrogen bond strength in a functionally significant way. Dimerization energies obtained from ab initio molecular orbital calculations on the hydrogen-bonded dimer of imidazole and planar formamide are used to represent the strength of this hydrogen bond in heme proteins. The effect of a change in iron oxidation state is modeled by varying the positive charge on imidazole. The effect of a change in hydrogen bond geometry is studied by employing x-ray coordinates for reduced and oxidized cytochrome c, deoxyand metmyoglobin, and deoxy-and methemoglobin. Our conclusions are that the strength of this hydrogen bond in heme proteins is sensitive to both the oxidation state of the iron atom and to geometry changes on the order of those obtained from the x-ray coordinates. We speculate that the changes in oxidation state may be functional y coupled with changes in hydrogen bond geometry and that this hydrogen bond represents a feasible pathway to link protein conformation with redox potential or reactivity of the iron atom. Imidazole rings of histidyl residues are bound to the metal in a large number of metalloproteins (1). In those proteins for which high resolution x-ray crystal structural data are available, the metal-bound imidazole rings are invariably found to be hydrogen bonded to electronegative groups on the apoprotein (2-4). The possibility that this hydrogen bond might link the tertiary structure of the protein with the reactivity of the metal has been recognized by several investigators, particularly in the case of heme proteins (5-12) in which the electronegative group is a backbone carbonyl oxygen.It is well known from studies of model compounds and of imidazole complexes of methemoglobin and metmyoglobin that the pKa of imidazole can drop several pH units upon complexation with a metal ion (1) [imidazole pKa = 14 (1), metmyoglobin imidazole pKa t 10 (13)]. It is also known that in general an increase in the oxidation state of a metal will result in a decrease in the pKa of coordinated imidazole (1). It thus seems an inescapable conclusion that a change in oxidation state of iron in a heme protein will affect the nature of this hydrogen bond to some degree. However, the significance of such an effect cannot be judged without some knowledge of the magnitude of the energies involved. This paper describes an approach to estimating the magnitudes of changes in such hydrogen bond energies in heme proteins, resulting from either (i) changes in the oxidation state of the metal, or (ii) changes in the hydrogen bond geometry due to changes in the tertiary structure of the protein.Estimates of energies are obtained from ab initio molecular orbital calculations of the dimeri...

Structural features promoting dioxygen production by Dechloromonas aromatica chlorite dismutase

“…2a). Hydrogen bonding of Glu-220 to the imidazole of His-170 lends anionic/imidazolate character to the proximal ligand (Scheme 1) [48]. A similar aspartate/histidine motif is widely observed in heme peroxidases [49], and has been shown to stabilize the iron in its reactive five-coordinate high-spin ferric state.…”

Redox control of proton transfers in membrane b-type cytochromes: an absorption and resonance Raman study on bis(imidazole) and bis(imidazolate) model complexes of iron-protoporphyrin

“…the bis (imidazole) and bis (imidazolate) complexes. Taking into account the fact that hydrogen donor strength of an ionizable grouping is directly correlated to its intrinsic acidity (Meot-Ner 1988), the pKa values obtained for the ionizations of axial ligands of Fe(II)-and Fe(III)-PP(ImH)2 indicate that the imidazole N1-H bonds of the ferric derivative are more polarizable by 3-4 orders of magnitude than those of the ferrous derivative• Thus, H-bonding at the coordinated imidazoles exerts its effect almost totally on the ferric heine and, hence, can decrease the redox potential of the corresponding Fe(II)/Fe(III) couple by 50 100 mV (Doeff et al 1983;Quinn et al 1983Quinn et al , 1984• As suggested by Valentine et al (1979), this differential mechanism probably constitutes an important factor in the fine tuning of oxidation-reduction potentials of cytochromes.…”

Just a Proton: Distinguishing the Two Electronic States of Five-Coordinate High-Spin Iron(II) Porphyrinates with Imidazole/ate Coordination

“…The strength of these hydrogen bonds is thought to vary from very weak proton donation to complete donation to form the imidazolate ligand 3–9. The notion that a strong hydrogen bond has a strong influence on heme protein behavior is longstanding but has been difficult to investigate in a systematic manner.…”