Understanding Rubredoxin Redox Potentials: Role of H-Bonds on Model Complexes

Abstract

The energetics of redox states in different models of rubredoxin-like iron-sulfur complexes (ISC) was computed using a combination of density functional and electrostatic continuum theories. In agreement with experiment, the calculated redox potential for the small ISC model [Fe(SCH2CH3)4](1-,2-) in acetonitrile was -813 mV [Galstyan, A. S.; Knapp, E. W. J. Comput. Chem. 2009, 30, 203-211] as compared to the measured value of -838 mV. Surprisingly the experimental values for rubredoxin (Rd) are much higher ranging between -87 and +39 mV. These large variations in redox potentials of ISC models and ISC in Rd are due to specific conformational symmetries adopted by the ligands due to both the protein environment and type and the number of H-bonds, and the dielectric environment. In a dielectric environment corresponding to proteins (ε = 20), the computed ISC redox potentials shift positive by about 64 mV for Fe-S···H-N and 95 mV for Fe-S···H-O H-bonds, correlating well with data estimated from experiments on ISC proteins. In aqueous solutions (ε = 80), a positive shift of 58 mV was computed for Fe-S···H-O H-bonds (using a model with the same ISC conformation as in Rd) in agreement with a measured value for Rd with partially solvent exposed ISC. The latter demonstrates the dependence of the ISC redox potentials on the environment (solvent or protein). For a model whose chemical composition is analog to the relevant part of ISC in a specific Rd, the computed redox potential of the model agrees with the measured value in Rd. This study allows to understand redox potential shifts for small ISC models and ISC in proteins.

Hybrid Dynamics Simulation Engine for Metalloproteins

“…Present in numerous forms of life, it exhibits backbone structural similarity and 50-60% sequence similarity among homologs. However, intriguingly, it covers a wide range of sequence-dependent reduction potentials, between À80 and þ40 mV (58), which found some rationalization in recent theoretical work by Knapp et al (59,60). Thus, rubredoxin and its mutants represent a simple and yet intricate model for revealing the strengths and limitations of our, to our knowledge, new method at a range of scales.…”

Terminal Electron–Proton Transfer Dynamics in the Quinone Reduction of Respiratory Complex I

“…A reference value of the UQ (MQ) Q/SQ redox couple was estimated to −188 mV (−241 mV) in water by B3LYP/def2-TZVP calculation, based on the experimental E m values of UQ and MQ in DMF and acetonitrile, 25 (Table S5) by the approach of Knapp and co-workers. 65−67 All our reported E m values are given relative to the NHE.…”

Parameters for molecular dynamics simulations of iron‐sulfur proteins

“…Here, we present the study of three of these proteins; two are mononuclear iron tetrahedral metal centers: rubredoxin (Rx) and desulforedoxin (Dx). Rx has a redox potential of −77mV and desulforedoxin of −35mV . The main difference between them is that, in rubredoxin, the iron is coordinated to two CXXC motifs, where C represents a cysteine and X two variable residues whereas, in desulforedoxin, the iron is coordinated to one CXXC motif and a CC motif (the cysteines are directly connected with no inner residues in between) as illustrated in Figure .…”