Relationship between oxygen affinity and autoxidation of myoglobin

Area of Science:

• Biochemistry
• Protein Chemistry
• Bioinorganic Chemistry

Background:

• Myoglobins are heme proteins crucial for oxygen transport and storage.
• Heme's electronic properties significantly influence protein function, including oxygen binding and stability.
• Understanding these relationships is key to protein engineering and drug design.

Purpose of the Study:

• To investigate the correlation between heme iron electron density and myoglobin's oxygen affinity and autoxidation rate.
• To explore the electronic factors governing the Fe(2+)-O(2) bond and its resonance with a Fe(3+)-O(2)(-) species.
• To elucidate how heme modifications impact oxygen dissociation and ligand binding.

Main Methods:

• Reconstitution of myoglobins with chemically modified heme cofactors.
• Spectroscopic analysis to probe electronic structure and ligand interactions.
• Kinetic studies to measure oxygen affinity and autoxidation rates.

Main Results:

• A strong correlation was observed between oxygen affinity and autoxidation rate, both decreasing with reduced heme iron electron density.
• Heme iron electron density influences the resonance between Fe(2+)-O(2) and Fe(3+)-O(2)(-) species.
• Shifts in resonance impact O(2) affinity by altering dissociation rates and accelerate autoxidation via increased H(+) affinity.

Conclusions:

• Heme iron electron density is a critical determinant of myoglobin's oxygen binding and oxidative stability.
• The electronic structure of the heme cofactor directly modulates the protein's functional properties.
• These findings provide insights into the mechanisms of oxygen transport and heme protein reactivity.