Main content area

Model of the MitoNEET [2Fe−2S] Cluster Shows Proton Coupled Electron Transfer

Bergner, Marie, Dechert, Sebastian, Demeshko, Serhiy, Kupper, Claudia, Mayer, James M., Meyer, Franc
Journal of the American Chemical Society 2017 v.139 no.2 pp. 701-707
Gibbs free energy, biomimetics, cysteine, dissociation, electron transfer, energy, histidine, iron, ligands, mitochondria, models, outer membrane proteins, respiratory rate
MitoNEET is an outer membrane protein whose exact function remains unclear, though a role of this protein in redox and iron sensing as well as in controlling maximum mitochondrial respiratory rates has been discussed. It was shown to contain a redox active and acid labile [2Fe–2S] cluster which is ligated by one histidine and three cysteine residues. Herein we present the first synthetic analogue with biomimetic {SN/S₂} ligation which could be structurally characterized in its diferric form, 5²–. In addition to being a high fidelity structural model for the biological cofactor, the complex is shown to mediate proton coupled electron transfer (PCET) at the {SN} ligated site, pointing at a potential functional role of the enzyme’s unique His ligand. Full PCET thermodynamic square schemes for the mitoNEET model 5²– and a related homoleptic {SN/SN} capped [2Fe–2S] cluster 4²– are established, and kinetics of PCET reactivity are investigated by double-mixing stopped-flow experiments for both complexes. While the NH bond dissociation free energy (BDFE) of 5H²– (230 ± 4 kJ mol–¹) and the free energy ΔG°PCET for the reaction with TEMPO (−48.4 kJ mol–¹) are very similar to values for the homoleptic cluster 4H²– (232 ± 4 kJ mol–¹, –46.3 kJ mol–¹) the latter is found to react significantly faster than the mitoNEET model (data for 5H²–: k = 135 ± 27 M–¹ s–¹, ΔH‡ = 17.6 ± 3.0 kJ mol–¹, ΔS‡ = −143 ± 11 J mol–¹ K–¹, and ΔG‡ = 59.8 kJ mol–¹ at 293 K). Comparison of the PCET efficiency of these clusters emphasizes the relevance of reorganization energy in this process.