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

Author:
Bergner, Marie, Dechert, Sebastian, Demeshko, Serhiy, Kupper, Claudia, Mayer, James M., Meyer, Franc
Source:
Journal of the American Chemical Society 2017 v.139 no.2 pp. 701-707
ISSN:
1520-5126
Subject:
Gibbs free energy, biomimetics, cysteine, dissociation, electron transfer, energy, histidine, iron, ligands, mitochondria, models, outer membrane proteins, respiratory rate
Abstract:
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.
Agid:
5614004