scholarly journals Local Electric Fields as a Natural Switch of Heme-Iron Protein Reactivity

2021 ◽  
Author(s):  
Daniel Bím ◽  
Anastassia N. Alexandrova
Keyword(s):  
Electric Fields ◽  
Protein Function ◽  
Active Sites ◽  
Axial Ligand ◽  
Heme Iron ◽  
Compound I ◽  
Field Range ◽  
Iron Protein ◽  
Axial Ligation ◽  
High Valent

Heme-iron oxidoreductases operating through the high-valent Fe<sup>IV</sup>O intermediates perform crucial and complicated transformations, such as oxidations of unreactive saturated hydrocarbons. These enzymes share the same Fe coordination, only differing by the axial ligation, e.g., Cys in P450 oxygenases, Tyr in catalases, and His in peroxidases. By examining ~200 heme-iron proteins, we show that the protein hosts exert highly specific intramolecular electric fields on the active sites, and there is a strong correlation between the direction and magnitude of this field and the protein function. In all heme proteins, the field is preferentially aligned with the Fe‒O bond (<b><i>F<sub>z</sub></i></b>). The Cys-ligated P450 oxygenases have the highest average <b><i>F<sub>z</sub></i></b> of 28.5 MV cm<sup>-1</sup>, i.e., most enhancing the oxyl-radical character of the oxo group, and consistent with the ability of these proteins to activate strong C‒H bonds. In contrast, in Tyr-ligated proteins, the average <b><i>F<sub>z</sub></i></b> is only 3.0 MV cm<sup>-1</sup>, apparently suppressing single-electron off-pathway oxidations, and in His-ligated proteins, <b><i>F<sub>z</sub></i></b> is –8.7 MV cm<sup>-1</sup>. The operational field range is given by the trade-off between the low reactivity of the Fe<sup>IV</sup>O Compound I at the more negative <b><i>F<sub>z</sub></i></b>, and the low selectivity at the more positive <b><i>F<sub>z</sub></i></b>. Consequently, a heme-iron site placed in the field characteristic of another heme-iron protein class loses its canonical function, and gains an adverse one. Thus, electric fields produced by the protein scaffolds, together with the nature of the axial ligand, control all heme-iron chemistry.

scholarly journals Local Electric Fields as a Natural Switch of Heme-Iron Protein Reactivity

2021 ◽  
Author(s):  
Daniel Bím ◽  
Anastassia N. Alexandrova
Keyword(s):  
Electric Fields ◽  
Protein Function ◽  
Active Sites ◽  
Axial Ligand ◽  
Heme Iron ◽  
Compound I ◽  
Field Range ◽  
Iron Protein ◽  
Axial Ligation ◽  
High Valent

Heme-iron oxidoreductases operating through the high-valent Fe<sup>IV</sup>O intermediates perform crucial and complicated transformations, such as oxidations of unreactive saturated hydrocarbons. These enzymes share the same Fe coordination, only differing by the axial ligation, e.g., Cys in P450 oxygenases, Tyr in catalases, and His in peroxidases. By examining ~200 heme-iron proteins, we show that the protein hosts exert highly specific intramolecular electric fields on the active sites, and there is a strong correlation between the direction and magnitude of this field and the protein function. In all heme proteins, the field is preferentially aligned with the Fe‒O bond (<b><i>F<sub>z</sub></i></b>). The Cys-ligated P450 oxygenases have the highest average <b><i>F<sub>z</sub></i></b> of 28.5 MV cm<sup>-1</sup>, i.e., most enhancing the oxyl-radical character of the oxo group, and consistent with the ability of these proteins to activate strong C‒H bonds. In contrast, in Tyr-ligated proteins, the average <b><i>F<sub>z</sub></i></b> is only 3.0 MV cm<sup>-1</sup>, apparently suppressing single-electron off-pathway oxidations, and in His-ligated proteins, <b><i>F<sub>z</sub></i></b> is –8.7 MV cm<sup>-1</sup>. The operational field range is given by the trade-off between the low reactivity of the Fe<sup>IV</sup>O Compound I at the more negative <b><i>F<sub>z</sub></i></b>, and the low selectivity at the more positive <b><i>F<sub>z</sub></i></b>. Consequently, a heme-iron site placed in the field characteristic of another heme-iron protein class loses its canonical function, and gains an adverse one. Thus, electric fields produced by the protein scaffolds, together with the nature of the axial ligand, control all heme-iron chemistry.

Ferric His93Gly myoglobin cavity mutant and its complexes with thioether and selenolate as heme protein models

2011 ◽  
Vol 15 (01) ◽  
pp. 29-38 ◽  
Author(s):  
Jing Du ◽  
Masanori Sono ◽  
John H. Dawson
Keyword(s):  
Active Sites ◽  
Magnetic Circular Dichroism ◽  
Sperm Whale ◽  
Heme Iron ◽  
Iron Protein ◽  
Protein Active Sites ◽  
Ligand Free ◽  
Ph Range ◽  
Protein Models ◽  
Exogenous Ligand

The composition of ferric exogenous ligand-free His93Gly sperm whale myoglobin (H93G Mb) at neutral pH has been determined by examination of the spectral properties of the protein over the pH range from 3.0 to 10.5. An apparent pKa value of ~6.6 has been observed for the conversion of a postulated six-coordinate bis-water-bound coordination structure at pH 5.0 to a five-coordinate hydroxide-bound form at pH 10.5. Starting from the exogenous ligand-free ferric H93G protein, ferric mono- and bis-thioether (tetrahydrothiophene, THT)-ligated adducts have been prepared and characterized by UV-visible (UV-vis) absorption and magnetic circular dichroism (MCD) spectroscopy. The mon-THT ferric H93G Mb species has hydroxide as the sixth ligand. The bis-THT derivative is a model for the low-spin ferric heme binding site of native bis-Met-ligated bacterioferritin or streptococcal heme-associated protein (Shp). A novel THT-bound ferryl H93G Mb moiety has been partially formed. The high-spin five-coordinate ferric H93G(selenolate) Mb complex has been prepared using benzeneselenol and characterized by UV-vis and MCD spectroscopy as a model for Se-Cys-ligated ferric cytochrome P450. The results described herein further demonstrate the versatility of the H93G cavity mutant for modeling the coordination structures of novel heme iron protein active sites.

scholarly journals Local Electric Fields As a Natural Switch of Heme-Iron Protein Reactivity

ACS Catalysis ◽  
2021 ◽  
pp. 6534-6546
Author(s):  
Daniel Bím ◽  
Anastassia N. Alexandrova
Keyword(s):  
Electric Fields ◽  
Heme Iron ◽  
Iron Protein

scholarly journals Large-area printing of ferroelectric surface and super-domains for efficient solar water splitting

2020 ◽  
Author(s):  
Yu Tian ◽  
Yaqing Wei ◽  
Minghui Pei ◽  
Rongrong Cao ◽  
Zhenao Gu ◽  
...  
Keyword(s):  
Water Splitting ◽  
Electric Fields ◽  
Electronic Structures ◽  
Active Sites ◽  
Large Area ◽  
Solar Water Splitting ◽  
High Efficient ◽  
Catalytic Sites ◽  
Order Of Magnitude ◽  
Magnitude Increase

Abstract Surface electronic structures of the photoelectrodes determine the activity and efficiency of the photoelectrochemical water splitting, but the controls of their surface structures and interfacial chemical reactions remain challenging. Here, we use ferroelectric BiFeO3 as a model system to demonstrate an efficient and controllable water splitting reaction by large-area constructing the hydroxyls-bonded surface. The up-shift of band edge positions at this surface enables and enhances the interfacial holes and electrons transfer through the hydroxyl-active-sites, leading to simultaneously enhanced oxygen and hydrogen evolutions. Furthermore, printing of ferroelectric super-domains with microscale checkboard up/down electric fields separates the distribution of reduction/oxidation catalytic sites, enhancing the charge separation and giving rise to an order of magnitude increase of the photocurrent. This large-area printable ferroelectric surface and super-domains offer an alternative platform for controllable and high-efficient photocatalysis.

scholarly journals The Role of Electrostatics in Enzymes: Do Biomolecular Force Fields Reflect Protein Electric Fields?

2020 ◽  
Author(s):  
Richard T Bradshaw ◽  
Jacek Dziedzic ◽  
Chris-Kriton Skylaris ◽  
Jonathan W. Essex
Keyword(s):  
Electric Fields ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Force Fields ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Polarizable Force Field ◽  
Polarizable Force Fields ◽  
Protein Active Sites ◽  
Dynamics Simulations

<div><div><div><p>Preorganization of large, directionally oriented, electric fields inside protein active sites has been proposed as a crucial contributor to catalytic mechanism in many enzymes, and may be efficiently investigated at the atomistic level with molecular dynamics simulations. Here we evaluate the ability of the AMOEBA polarizable force field, as well as the additive Amber ff14SB and Charmm C36m models, to describe the electric fields present inside the active site of the peptidyl-prolyl isomerase cyclophilin A. We compare the molecular mechanical electric fields to those calculated with a fully first principles quantum mechanical (QM) representation of the protein, solvent, and ions, and find that AMOEBA consistently shows far greater correlation with the QM electric fields than either of the additive force fields tested. Catalytically-relevant fields calculated with AMOEBA were typically smaller than those observed with additive potentials, but were generally consistent with an electrostatically-driven mechanism for catalysis. Our results highlight the accuracy and the potential advantages of using polarizable force fields in systems where accurate electrostatics may be crucial for providing mechanistic insights.</p></div></div></div>

The Structure of a Non-Heme Iron Protein: Rubredoxin at 1.5 A Resolution

1972 ◽  
Vol 36 (0) ◽  
pp. 359-367 ◽  
Author(s):  
K. D. Watenpaugh ◽  
L. C. Sieker ◽  
J. R. Herriott ◽  
L. H. Jensen
Keyword(s):  
Heme Iron ◽  
Iron Protein ◽  
Non Heme Iron

scholarly journals Supramolecular Stark Effect in Host-Guest Complexes via Charge Density Analysis

2014 ◽  
Vol 70 (a1) ◽  
pp. C674-C674
Author(s):  
Sajesh Thomas ◽  
Rebecca Fuller ◽  
Alexandre Sobolev ◽  
Philip Schauer ◽  
Simon Grabowsky ◽  
...  
Keyword(s):  
Electric Field ◽  
Charge Density ◽  
Electric Fields ◽  
Active Sites ◽  
Stark Effect ◽  
Dipole Moments ◽  
Covalent Bonds ◽  
Guest Molecules ◽  
Density Mapping ◽  
Density Analysis

The effect of an electric field on the vibrational spectra, the Vibrational Stark Effect (VSE), has been utilized extensively to probe the local electric field in the active sites of enzymes [1, 2]. For this reason, the electric field and consequent polarization effects induced by a supramolecular host system upon its guest molecules attain special interest due to the implications for various biological processes. Although the host-guest chemistry of crown ether complexes and clathrates is of fundamental importance in supramolecular chemistry, many of these multicomponent systems have yet to be explored in detail using modern techniques [3]. In this direction, the electrostatic features associated with the host-guest interactions in the inclusion complexes of halogenated acetonitriles and formamide with 18-crown-6 host molecules have been analyzed in terms of their experimental charge density distribution. The charge density models provide estimates of the molecular dipole moment enhancements which correlate with the simulated values of dipole moments under electric field. The accurate electron density mapping using the multipole formalism also enable the estimation of the electric field experienced by the guest molecules. The electric field vectors thus obtained were utilized to estimate the vibrational stark effect in the nitrile (-C≡N) and carbonyl (C=O) stretching frequencies of the guest molecules via quantum chemical calculations in gas phase. The results of these calculations indicate remarkable elongation of C≡N and C=O bonds due to the electric fields. The electronic polarization in these covalent bonds induced by the field manifests as notable red shifts in their characteristic vibrational frequencies. These results derived from the charge densities are further supported by FT-IR experiments and thus establish the significance of a phenomenon that could be termed as the "supramolecular Stark effect" in crystal environment.

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