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How cytochromes with different folds control heme redox potentials
Junjun Mao1, Karin Hauser, M R Gunner
1Physics Department J-419, City College of New York, 138th Street and Convent Avenue, New York, New York 10031, USA.
Biochemistry
|August 20, 2003
Summary
This study used multiconformation continuum electrostatics (MCCE) to calculate midpoint potentials (E(m)) for 13 cytochromes. Protein environment significantly influences E(m) by altering heme solvation and through specific amino acid interactions.
Area of Science:
- Biochemistry
- Computational Chemistry
- Structural Biology
Background:
- Cytochromes are crucial electron transfer proteins with diverse heme-binding motifs.
- Understanding the factors that modulate cytochrome midpoint potentials (E(m)) is key to their functional characterization.
- Previous studies have explored E(m) variations, but a comprehensive computational analysis across different cytochrome classes was lacking.
Purpose of the Study:
- To calculate and analyze the electrochemical midpoint potentials (E(m)) of 13 diverse cytochromes using a computational approach.
- To identify and quantify the contributions of protein environment factors to cytochrome E(m) variations.
- To predict the solution E(m) for specific heme ligation environments in cytochromes c' and f.
Main Methods:
- Utilized multiconformation continuum electrostatics (MCCE) to compute E(m) values for 13 cytochromes with varying heme motifs (globin, four-helix bundle, alpha beta roll, beta sandwich).
- MCCE calculates the change in oxidation free energy by modeling the heme-axial ligand complex in both water and protein environments.
- Simultaneously sampled protein conformational states, ionization states of titratable residues, and heme redox states.
Main Results:
- Calculated E(m) values showed good agreement with experimental data for cytochromes with His-Met and bis-His ligated hemes.
- Protein environments significantly increase E(m) (130-260 mV) compared to solvated hemes due to reduced solvation energy, independent of heme exposure.
- Specific interactions like backbone amide dipoles and buried side chains generally raise E(m), while heme propionates lower it, contributing to pH dependence.
Conclusions:
- The protein environment plays a dominant role in determining cytochrome E(m), with specific structural features like amide dipoles and buried residues significantly impacting redox potential.
- Heme propionates contribute to the pH dependence of E(m) through proton release upon oxidation.
- The study predicts specific solution E(m) ranges for cytochromes c' and f based on their heme ligation and protein environment.