Paper Citing NAMD - Abstract
Harris, Travis V.; Morokuma, Keiji
QM/MM Structural and Spectroscopic Analysis of the Di-iron(II) and Di-iron(III) Ferroxidase Site in M Ferritin
INORGANIC CHEMISTRY, 52:8551-8563, AUG 5 2013
Ferritins are cage-like proteins composed of 24 subunits that take up iron(II) and store it as an iron(III) oxide mineral core. A critical step is the ferroxidase reaction, in which oxygen reacts with a di-iron(II) site, proceeding through a peroxo intermediate, to form mu-oxo/hydroxo-bridged di-iron(III) products. The recent crystal structures of copper(II)- and iron(III)bound frog M ferritin at 2.8 angstrom resolution [Bertini; et al J. Am. Chem. Soc. 2012, 134, 6169-6176] provided an opportunity to theoretically investigate the detailed structures of the reactant state and products In this study, the quantum mechanical/molecular mechanical ONIOM method is used to structurally optimize a series of single-subunit models with various hydration, protonation, and coordination states of the ferroxidase site Calculated exchange coupling constants (1), Mossbauer parameters, and time-dependent density functional theoretical (TD-DFT) circular dichroism spectra with electronic embedding are compared with the available experimental data The di-iron(II) model with the most experimentally consistent structural and spectroscopic parameters has S-coordinate iron centers with Glu23, Glu58, His61, and two waters completing one coordination sphere, and His54, Glu58, Glu103, and Asp140 completing the other. In contrast to a previously proposed structure, Gln137 is not directly coordinated, but it is involved in hydrogen bonding with several iron ligands. For the di-iron(III) products, we find that a mu-oxo-bridged and two doubly bridged (mu-hydroxo and mu-oxo/hydroxo) species are likely coproduced. Although four quadrupole doublets were observed experimentally, we find that two doublets may arise from a single asymmetrically coordinated ferroxidase site These proposed key structures will help to explore the pathway connecting the di-Fe(II) state to the peroxo intermediate and the branching mechanisms leading to the multiple products.
