Heme electron transfer in peroxidases: the propionate e-pathway

Area of Science:

• Biochemistry
• Computational Chemistry
• Structural Biology

Background:

• Heme peroxidases feature unique heme propionate arrangements.
• The role of these propionates in electron transfer is not fully understood.

Purpose of the Study:

• To investigate the involvement of heme propionate side chains in electron transfer pathways.
• To elucidate the mechanism of substrate oxidation in ascorbate peroxidase and inter-heme electron transfer in cytochrome c peroxidase.

Main Methods:

• Utilized mixed quantum mechanical/molecular mechanics (QM/MM) calculations.
• Employed selective activation/deactivation of quantum regions to map electron transfer pathways.

Main Results:

• Identified an electron transfer pathway directly involving the porphyrin ring and heme propionates.
• Demonstrated that substrate presence is crucial for activating the electron transfer channel in ascorbate peroxidase.
• Proposed a novel mechanism termed the "propionate e-pathway".

Conclusions:

• Heme propionates play a direct role in electron transfer, not just electrostatic anchoring.
• The "propionate e-pathway" may be a general motif for heme-group electron transfer.
• Substrate interaction significantly influences electron transfer dynamics in heme peroxidases.