Computational Insights into Five- versus Six-Coordinate Iron Center in Ferrous Soybean Lipoxygenase

Soybean lipoxygenase (SLO) serves
as a prototype for fundamental
understanding of hydrogen tunneling in enzymes. Its reactivity depends
on the active site structure around a mononuclear, nonheme iron center.
The available crystal structures indicate five-coordinate iron, while
magnetic circular dichroism experiments suggest significant populations
of both five-coordinate (5C) and six-coordinate (6C) iron in ferrous
SLO. Quantum mechanical calculations of gas phase models produce only
6C geometries. Herein mixed quantum mechanical/molecular mechanical
(QM/MM) calculations are employed to identify and characterize the
5C and 6C geometries. These calculations highlight the importance
of the protein environment, particularly two Gln residues in a hydrogen-bonding
network with Asn694, the ligand that can dissociate. This hydrogen-bonding
network is similar in both geometries, but twisting of a dihedral
angle in Asn694 moves its oxygen away from the iron in the 5C geometry.
These insights are important for future simulations of SLO.