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

• Published in: Journal of the American Chemical Society Vol. 139; no. 2; pp. 701 - 707
• Main Authors: Bergner, Marie, Dechert, Sebastian, Demeshko, Serhiy, Kupper, Claudia, Mayer, James M, Meyer, Franc
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.01.2017
• Subjects: biomimetics; cysteine; dissociation; electron transfer; Electron Transport; energy; Gibbs free energy; histidine; iron; ligands; Membrane Proteins - chemistry; mitochondria; Mitochondrial Proteins - chemistry; Models, Biological; outer membrane proteins; Oxidation-Reduction; Protons; respiratory rate
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.6b09180

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, 5 2– . 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 5 2– and a related homoleptic {SN/SN} capped [2Fe–2S] cluster 4 2– 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 5H 2– (230 ± 4 kJ mol–1) and the free energy Δ G° PCET for the reaction with TEMPO (−48.4 kJ mol–1) are very similar to values for the homoleptic cluster 4H 2– (232 ± 4 kJ mol–1, –46.3 kJ mol–1) the latter is found to react significantly faster than the mitoNEET model (data for 5H 2– : 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.