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Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study.

ABSTRACT: The effect of distal histidine on ligation of NO to ferrous and ferric-heme, has been investigated with the high-level density functional theoretical (DFT) method. It has been predicted that the distal histidine significantly stabilizes the interaction of NO ferrous-heme (by -2.70 kcal mol^-1). Also, water hydrogen bonding is quite effective in strengthening the Fe-NO bond in ferrous heme. In contrast in ferric heme, due to the large distance between the H₂O and O(NO) and lack of hydrogen bonding, the distal histidine exhibits only a slight effect on the binding of NO to the ferric analogue. Concerning the bond nature of Fe^II-NO and Fe^III-NO in heme, a QTAIM analysis predicts a partially covalent and ionic bond nature in both systems.

SUBMITTER: Fateminasab F

PROVIDER: S-EPMC8981399 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study.

Fateminasab Fatemeh F de la Lande Aurelien A Omidyan Reza R

RSC advances 20220208 8

The effect of distal histidine on ligation of NO to ferrous and ferric-heme, has been investigated with the high-level density functional theoretical (DFT) method. It has been predicted that the distal histidine significantly stabilizes the interaction of NO ferrous-heme (by -2.70 kcal mol<sup>-1</sup>). Also, water hydrogen bonding is quite effective in strengthening the Fe-NO bond in ferrous heme. In contrast in ferric heme, due to the large distance between the H<sub>2</sub>O and O(NO) and la ...[more]

PMID: 35425484

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Project description:Cytochrome-c-peroxidase (CCP) contains a five-coordinate heme active site. The reduction potential for the ferric to ferrous couple in CCP is anomalously low and pH dependent (Eo = ~-180 mV vs. S.H.E. at pH 7). The contribution of the protein environment to the tuning of the redox potential of this couple is evaluated using site directed mutants of several amino acid residues in the environment of the heme. These include proximal pocket mutation to residues Asp-235, Trp-191, Phe-202 and His-175, distal pocket mutation to residues Trp-51, His-52, and Arg-48; and a heme edge mutation to Ala-147. Where unknown, the structural changes resulting from the amino acid substitution have been studied by X-ray crystallography. In most cases, ostensibly polar or charged residues are replaced by large hydrophobic groups or alternatively by Ala or Gly. These latter have been shown to generate large, solvent filled cavities. Reduction potentials are measured as a function of pH by spectroelectrochemistry. Starting with the X-ray derived structures of CCP and the mutants, or with predicted structures generated by Molecular Dynamics (MD), predictions of redox potential changes are modeled using the Protein Dipoles Langevin Dipoles (PDLD) method. These calculations serve to model an electrostatic assessment of the redox potential change with simplified assumptions about heme iron chemistry, with the balance of the experimentally observed shifts in redox potential being thence attributed to changes in the ligand set and heme coordination chemistry, and/or other changes in the structure not directly evident in the X-ray structures (e.g. ionization states, specific roles played by solvent species, or conformationally flexible portions of the protein). Agreement between theory and experiment is good for all mutant proteins with the exception of the mutation Arg 48 to Ala, and His 52 to Ala. In the former case, the influence of phosphate buffer is adduced to account for the discrepancy, and measurements made in a bis-tris propane/2-(N-morpholino)ethanesulfonic acid buffer system agree well with theory. For the latter case, an unknown structural element relevant to His-52, and/or solvent influence in the mutant akin to anion binding in the distal pocket (though lacking proof that it is) manifests in this mutant. The use of exogenous (sixth) ligands in dissecting the contributions to control of redox potential are also explored as a pathway for model building.

Dataset Information

Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study.

Publications

Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study.

Similar Datasets

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