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. 1979 Mar;76(3):1009–1013. doi: 10.1073/pnas.76.3.1009

Coupling between oxidation state and hydrogen bond conformation in heme proteins

Joan S Valentine *, Robert P Sheridan †, Leland C Allen ‡, Peter C Kahn §
PMCID: PMC383176  PMID: 220604

Abstract

In all heme proteins for which crystal structures are available, the Nε of a histidyl residue is bonded to the heme iron and Nδ 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, deoxy- and 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 functionally 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.

Keywords: cytochrome c, hemoglobin, myoglobin, cooperativity, histidine

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Selected References

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