Proton-coupled electron transfer in soybean lipoxygenase

Area of Science:

• Biochemistry
• Quantum Chemistry
• Enzyme Catalysis

Background:

• Proton-coupled electron transfer (PCET) is crucial in biological systems.
• Soybean lipoxygenase-1 (SLO-1) is a key enzyme involved in lipid metabolism.
• Understanding the mechanisms of SLO-1 catalysis is essential for biochemical research.

Purpose of the Study:

• To investigate the PCET reaction mechanism catalyzed by soybean lipoxygenase-1.
• To elucidate the roles of quantum mechanical tunneling and vibrational motion in the reaction.
• To analyze the temperature dependence of reaction rates and kinetic isotope effects.

Main Methods:

• Multistate continuum theory to model proton transfer.
• Density functional theory (DFT) for inner-sphere reorganization energy.
• Frequency-resolved cavity model for outer-sphere reorganization energy.
• Docking simulations for protein conformations.

Main Results:

• Calculated rates and kinetic isotope effects agree with experimental data.
• Weak temperature dependence of rates is attributed to a small free energy barrier.
• High deuterium kinetic isotope effect (81) explained by vibrational wave function overlap and vibronic states.
• Proton donor-acceptor distance significantly smaller than equilibrium distance.

Conclusions:

• Quantum mechanical treatment of proton transfer is vital for understanding SLO-1 catalysis.
• Vibrational motion plays a critical role in optimizing the donor-acceptor distance for efficient PCET.
• The study provides a detailed molecular-level understanding of the SLO-1 reaction mechanism.