Coupling between oxidation state and hydrogen bond conformation in heme proteins

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Heme proteins feature a conserved histidyl residue coordinating the heme iron via N(epsilon).
• This histidyl residue's N(delta) forms a hydrogen bond with a peptide backbone carbonyl oxygen.
• The functional significance of variations in this hydrogen bond's strength is under investigation.

Purpose of the Study:

• To investigate if changes in iron oxidation state or hydrogen bond geometry affect hydrogen bond strength.
• To determine if these changes are functionally significant in heme proteins.
• To explore the link between protein conformation and iron atom's redox potential or reactivity.

Main Methods:

• Ab initio molecular orbital calculations were used to determine dimerization energies of imidazole and formamide.
• These calculations modeled the strength of the hydrogen bond in heme proteins.
• X-ray coordinates of reduced/oxidized cytochrome c, deoxy/metmyoglobin, and deoxy/methemoglobin were analyzed to study geometry changes.

Main Results:

• The hydrogen bond strength is sensitive to the iron atom's oxidation state.
• Hydrogen bond strength is also sensitive to geometry changes observed in experimental structures.
• Calculations showed that varying positive charge on imidazole (modeling iron oxidation) impacts hydrogen bond strength.

Conclusions:

• The studied hydrogen bond's strength is significantly influenced by both iron oxidation state and geometric factors.
• These findings suggest a functional coupling between redox state changes and hydrogen bond geometry.
• This hydrogen bond serves as a potential mechanism linking protein conformation to the iron atom's redox properties.