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Electron Paramagnetic Resonance Spectroscopy as a Probe of Hydrogen Bonding in Heme-Thiolate Proteins.
- Source :
-
Inorganic chemistry [Inorg Chem] 2019 Dec 02; Vol. 58 (23), pp. 16011-16027. Date of Electronic Publication: 2019 Nov 15. - Publication Year :
- 2019
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Abstract
- Despite utilizing a common cofactor binding motif, hemoproteins bearing a cysteine-derived thiolate ligand (heme-thiolate proteins) are involved in a diverse array of biological processes ranging from drug metabolism to transcriptional regulation. Though the origin of heme-thiolate functional divergence is not well understood, growing evidence suggests that the hydrogen bonding (H-bonding) environment surrounding the Fe-coordinating thiolate influences protein function. Outside of X-ray crystallography, few methods exist to characterize these critical H-bonding interactions. Electron paramagnetic resonance (EPR) spectra of heme-thiolate proteins bearing a six-coordinate, Fe(III) heme exhibit uniquely narrow low-spin ( S = 1/2), rhombic signals, which are sensitive to changes in the heme-thiolate H-bonding environment. To establish a well-defined relationship between the magnitude of g -value dispersion in this unique EPR signal and the strength of the heme-thiolate H-bonding environment, we synthesized and characterized of a series of six-coordinate, aryl-thiolate-ligated Fe(III) porphyrin complexes bearing a tunable intramolecular H-bond. Spectroscopic investigation of these complexes revealed a direct correlation between H-bond strength and g -value dispersion in the rhombic EPR signal. Using density functional theory (DFT), we elucidated the electronic origins of the narrow, rhombic EPR signal in heme-thiolates, which arises from an Fe-S p <subscript>π</subscript> -d <subscript>π</subscript> bonding interaction. Computational analysis of the intramolecularly H-bonded heme-thiolate models revealed that H-bond donation to the coordinating thiolate reduces thiolate donor strength and weakens this Fe-S interaction, giving rise to larger g -value dispersion. By defining the relationship between heme-thiolate electronic structure and rhombic EPR signal, it is possible to compare thiolate donor strengths among heme-thiolate proteins through analysis of low-spin, Fe(III) EPR spectra. Thus, this study establishes EPR spectroscopy as a valuable tool for exploring how second coordination sphere effects influence heme-thiolate protein function.
Details
- Language :
- English
- ISSN :
- 1520-510X
- Volume :
- 58
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Inorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31786931
- Full Text :
- https://doi.org/10.1021/acs.inorgchem.9b02506