Density Functional Theory Calculations on the Fe₂S₂(Arg)(SCys)(SSCys)₂ Cluster in HydE: Unique Electronic Structure and Redox Properties

A Fe₂S₂ cluster with unprecedented CysSS⁻ (cysteinepersulfide) coordination has been observed crystallographically in the AdoMet-dependent hydrogenase maturase enzyme HydE. Geometry-optimized density functional theory calculations are used to develop an electronic structure description of this unusual cluster. The results indicate that the CysSS⁻ ligand is unique because it can act as a donor as well as an acceptor ligand. This is due to the presence of S−S π* (occupied) and S−S σ* (unoccupied) orbitals in this ligand. Extensive back-bonding is observed between the cluster and the S−S σ* orbital. The back-bonding is significantly higher in the reduced state, which is calculated to shift the reduction potential of this Fe₂S₂ cluster by +400 mV in the gas phase relative to a CysS⁻-coordinated Fe₂S₂ cluster model of BioB.