title: Model of the MitoNEET [2Fe-2S] Cluster Shows Proton Coupled Electron Transfer.
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°PCETfor 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-1s-1, ΔH‡= 17.6 ± 3.0 kJ mol-1, ΔS‡= -143 ± 11 J mol-1K-1, and ΔG‡= 59.8 kJ mol-1at 293 K). Comparison of the PCET efficiency of these clusters emphasizes the relevance of reorganization energy in this process.
authors.affiliation: Institute of Inorganic Chemistry, Georg-August-University Göttingen , Tammannstraße 4, D-37077 Göttingen, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Bergner
authors.affiliation: Institute of Inorganic Chemistry, Georg-August-University Göttingen , Tammannstraße 4, D-37077 Göttingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dechert
authors.affiliation: Institute of Inorganic Chemistry, Georg-August-University Göttingen , Tammannstraße 4, D-37077 Göttingen, Germany.
authors.forename: Serhiy
authors.initials: S
authors.lastname: Demeshko
authors.affiliation: Institute of Inorganic Chemistry, Georg-August-University Göttingen , Tammannstraße 4, D-37077 Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kupper
authors.affiliation: Yale University , 225 Prospect Street, New Haven, Connecticut 06511, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Mayer
authors.affiliation: Institute of Inorganic Chemistry, Georg-August-University Göttingen , Tammannstraße 4, D-37077 Göttingen, Germany.
authors.forename: Franc
authors.identifier: 0000-0002-8613-7862
authors.initials: F
authors.lastname: Meyer
mesh_terms: D004579:Electron Transport; D008565:Membrane Proteins / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000737:chemistry*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011522:Protons
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011522:Protons