Heme protein oxygen affinity regulation exerted by proximal effects

Area of Science:

• Biochemistry
• Computational Chemistry
• Structural Biology

Background:

• Heme proteins are vital in all organisms, performing diverse functions often involving diatomic ligand binding (O(2), CO, NO).
• Precise regulation of ligand affinity is critical for heme protein function.
• This regulation involves protein-ligand interactions and intrinsic heme reactivity tuning.

Purpose of the Study:

• To investigate the proximal regulation of oxygen affinity in Fe(II) histidine coordinated heme proteins.
• To analyze the impact of proximal histidine's charge donation, rotational position, and distance to the heme plane on oxygen binding.
• To elucidate the cooperative effects of these proximal factors on oxygen affinity.

Main Methods:

• Utilized Density Functional Theory (DFT) calculations on heme model systems.
• Employed hybrid quantum-classical (QM-MM) calculations on myoglobin and leghemoglobin.
• Analyzed three key proximal effects: charge donation, rotational position, and distance.

Main Results:

• All three proximal histidine effects (charge donation, rotation, distance) cooperatively tune the Fe-O(2) bond strength.
• Computational findings align with experimental data on oxygen affinity.
• Demonstrated the interplay between proximal histidine and heme group reactivity.

Conclusions:

• Proximal histidine plays a significant role in modulating oxygen affinity in heme proteins.
• These proximal effects are essential for understanding oxygen binding in various heme proteins, often in conjunction with distal effects.
• Provides insights into the molecular mechanisms governing heme protein function and ligand binding specificity.