Distinguishing the Protonation State of the Histidine Ligand to the Oxidized Iron-Sulfur Cluster from the MitoNEET Family of Proteins.

The iron-sulfur cluster located in the recently discovered human mitoNEET protein (and related proteins) is structurally similar to the more well-known ferredoxin and Rieske clusters. Although its biological function is uncertain, the iron-sulfur cluster in mitoNEET has been proposed to undergo proton-coupled electron transfer involving the histidine ligand to the cluster. The cluster is also released from the protein at low pH. This contribution reports density functional calculations to model the structures, vibrations, and Heisenberg coupling constants (J) for high-spin (HS), broken symmetry (BS) singlet, and extended broken symmetry (EBS) singlet states of the oxidized iron-sulfur cluster from mitoNEET. This work suggests that J values or N isotopic frequency shifts may provide methods for determining experimentally whether the histidine ligand to the oxidized iron-sulfur cluster in human mitoNEET and mitoNEET-related proteins is protonated or deprotonated.