11/21 – Pengfei Li, Loyola University Chicago

This is an in-person event in room COMRB 8175 on west campus (directions).  You can also watch seminar live here>>

Speaker:
Pengfei Li, PhD
Department of Chemistry and Biochemistry
Loyola University Chicago

Title:
Theoretical Modeling of Proton-Coupled Electron Transfer in Soybean Lipoxygenase

Abstract:

Proton-coupled electron transfer (PCET) plays important roles in many chemical, biochemical, and energy conversion processes. However, modeling of these processes is challenging due to the quantum nature of proton. This talk will give a brief introduction about the PCET theory, as well as its application on soybean lipoxygenase. The PCET reaction catalyzed by soybean lipoxygenase serves as a prototype for understanding hydrogen tunneling in enzyme catalysis. Specifically, it exhibits a surprisingly large kinetic isotope effect (KIE) of ~80, and mutations of residues in the substrate binding pocket significantly modulate this KIE and its temperature dependence. In the extreme case, the L546A/L754A mutant exhibits a KIE ~600. Aided by MCPB.py, a program developed by the speaker that has been distributed through the AMBER software package and could significantly facilitate the force field parameterization of metal sites in metalloproteins and organometallic compounds, we have studied the soybean lipoxygenase and its mutants by using the quantum mechanical/molecular mechanical (QM/MM) method and classical molecular dynamics simulations. Our study has identified the roles of substrate binding mode, electric field, and mutations in the substrate binding pocket on regulating hydrogen tunneling in the enzyme catalysis. The resulting insights may be useful in guiding relevant enzyme and molecular design efforts.