Electrostatic effects in hemoglobin: hydrogen ion equilibria in human deoxy- and oxyhemoglobin A

Area of Science:

• Biophysics
• Protein Chemistry
• Biochemistry

Background:

• Electrostatic interactions are crucial for protein function.
• Hemoglobin undergoes significant structural changes upon oxygen binding.
• Understanding these changes is key to deciphering hemoglobin's physiological roles.

Purpose of the Study:

• To apply the modified Tanford-Kirkwood theory to human deoxyhemoglobin and oxyhemoglobin.
• To investigate the hydrogen ion equilibria and electrostatic interactions in both states.
• To compare theoretical predictions with experimental data.

Main Methods:

• Utilized atomic coordinates of deoxyhemoglobin and generated oxyhemoglobin structures.
• Employed the modified Tanford-Kirkwood theory incorporating charged residue positions and solvent accessibility.
• Calculated theoretical titration curves and pK values.

Main Results:

• Theoretical titration curves closely matched experimental potentiometric data.
• Predicted pK values at half-titration aligned with observed values for both hemoglobin states.
• Demonstrated the cumulative impact of electrostatic interactions and quaternary transition on ionizable groups.

Conclusions:

• The modified Tanford-Kirkwood theory accurately models electrostatic interactions in hemoglobin.
• Changes in static solvent accessibility during the quaternary transition significantly affect ionizable groups.
• Electrostatic interactions play a vital role in hemoglobin's functional mechanism.