Experimental and Computational Insight into the Mechanism of NO Binding to Ferric Microperoxidase. The Likely Role of Tautomerization to Account for the pH Dependence

Oszajca, Maria; Drabik, Gabriela; Radoń, Mariusz; Franke, Alicja; Eldik, Rudi van; Stochel, Grażyna

doi:10.1021/acs.inorgchem.1c00933

Cited by 12 publications

(35 citation statements)

References 107 publications

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“…The complex possessing the same spectra can be obtained by the addition of NO to the ferrous-AcMP-11 ( Figure S4 ) and also as a product of reductive nitrosylation occurring after NO binding by ferric-AcMP-11 under basic conditions. 30 For clarity, the representative transformation of I 1 to (AcMP-11)Fe 2+ (NO) was illustrated separately in Figure 2 B. When the analogous reactions were carried out with (AcMP-11)Fe 3+ (AcCys) or (AcMP-11)Fe 3+ (Cys), similar spectral changes were registered.…”

Section: Resultsmentioning

confidence: 87%

“…Dependencies of k obs 1 (A) in a function of NO concentration in the presence of 3 mM [RS] T and (B) in a function of [GSH] T in the presence of 0.36 mM NO. The solid lines represent the results of simulations obtained using rate constants reported in Table S1 and obtained previously ( k on NO = 3.7 × 10 6 M –1 s –1 , k off NO = 3.4 s –1 at 20 C°) . Experimental conditions: [AcMP-11] = 5 × 10 –6 M, [phosphate buffer] = 0.1 M, [DTPA] = 0.25 mM, pH = 7.4, T = 20 °C.…”

Section: Resultsmentioning

confidence: 98%

“…Figure 2 C illustrates the representative transformation of (AcMP-11)Fe 2+ (NO + ) after mixing with AcCys to the transient intermediate. The initial spectrum of (AcMP-11)Fe 2+ (NO + ) (green—λ max = 415, 527, and 561 nm) 30 was slightly blue-shifted, indicating the formation of an intermediate with UV–vis spectral features (λ max 413 nm and broad Q band at 522–566 nm, Figure 2 C red spectrum) analogous to the ones registered for I 1 in the reaction of (AcMP-11)Fe 3+ (RS) with NO (compare Figure 2 A,C). Also in this case, the transient intermediate was converted to a ferrous-nitrosyl complex ( Figure 2 D).…”

Section: Resultsmentioning

confidence: 99%

“…The solid lines represent the results of simulations obtained using rate constants reported in Table S1 and obtained previously ( k on NO = 3.7 × 10 6 M –1 s –1 , k off NO = 3.4 s –1 at 20 C°). 30 Experimental conditions: [AcMP-11] = 5 × 10 –6 M, [phosphate buffer] = 0.1 M, [DTPA] = 0.25 mM, pH = 7.4, T = 20 °C.…”

Section: Resultsmentioning

confidence: 99%

“…Alternatively, deoxygenated AcMP-11 (5 × 10 Theoretical Calculations. Two theoretical models of AcMP-11 were used for the study: a simplified model in which the heme moiety was reduced to Fe 3+ porphin with imidazole as an axial ligand (referred to as model 1) and a full model consisting of the heme group, its side substituents, a part of the peptide backbone (Cys14-Ala15-Gln16-Cys17-His18), and explicit water molecules as developed previously 30 (referred to as model 2)�see the Computational Analysis of N-and S-Iron-Heme-Coordinated S-Nitrosothiols section. The geometry and electronic properties of the possible complexes of AcMP-11 with NO, selected thiols (Cys, AcCys, GSH, and their simplified form modeled by the −SCH 3 − group), and nitrosothiols (bound via different donor atoms�S and N) were elucidated.…”

Section: Methodsmentioning

confidence: 99%

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Unraveling the Molecular Mechanism of S-Nitrosation Mediated by N-Acetylmicroperoxidase-11

et al. 2023

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Conversion of NO to stable S-nitrosothiols is perceived as a biologically important strategy of NO storage and a signal transduction mechanism. Transition-metal ions and metalloproteins are competent electron acceptors that may promote the formation of S-nitrosothiols from NO. We selected N-acetylmicroperoxidase (AcMP-11), a model of protein heme centers, to study NO incorporation to three biologically relevant thiols (glutathione, cysteine, and N-acetylcysteine). The efficient formation of S-nitrosothiols under anaerobic conditions was confirmed with spectrofluorimetric and electrochemical assays. AcMP-11-assisted incorporation of NO to thiols occurs via an intermediate characterized as an N-coordinated S-nitrosothiol, (AcMP-11)Fe 2+ (N(O)SR), which is efficiently converted to (AcMP-11)Fe 2+ (NO) in the presence of NO excess. Two possible mechanisms of S-nitrosothiol formation at the heme-iron were considered: a nucleophilic attack on (AcMP-11)Fe 2+ (NO + ) by a thiolate and a reaction of (AcMP-11)Fe 3+ (RS) with NO. Kinetic studies, performed under anaerobic conditions, revealed that the reversible formation of (AcMP-11)Fe 2+ (N(O)SR) occurs in a reaction of RS − with (AcMP-11)Fe 2+ (NO + ) and excluded the second mechanism, indicating that the formation of (AcMP-11)Fe 3+ (RS) is a dead-end equilibrium. Theoretical calculations revealed that N-coordination of RSNO to iron, forming (AcMP-11)Fe 2+ (N(O)SR), shortens the S−N bond and increases the complex stability compared to S-coordination. Our work unravels the molecular mechanism of heme-iron-assisted interconversion of NO and low-molecular-weight thiols to S-nitrosothiols and recognizes the reversible NO binding in the form of a heme-Fe 2+ (N(O)SR) motif as an important biological strategy of NO storage.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Unraveling the Molecular Mechanism of S-Nitrosation Mediated by N-Acetylmicroperoxidase-11

et al. 2023

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A Personal Account on Inorganic Reaction Mechanisms

Polaczek,

Kieca,

Oszajca

et al. 2023

The Chemical Record

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The presented Review is focused on the latest research in the field of inorganic chemistry performed by the van Eldik group and his collaborators. The first part of the manuscript concentrates on the interaction of nitric oxide and its derivatives with biologically important compounds. We summarized mechanistic information on the interaction between model porphyrin systems (microperoxidase) and NO as well as the recent studies on the formation of nitrosylcobalamin (CblNO). The following sections cover the characterization of the Ru(II)/Ru(III) mixed‐valence ion‐pair complexes, including Ru(II)/Ru(III)(edta) complexes. The last part concerns the latest mechanistic information on the DFT techniques applications. Each section presents the most important results with the mechanistic interpretations.

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Chelate Complexes of 3d Transition Metal Ions─A Challenge for Electronic-Structure Methods?

Hehn,

Deglmann,

Kühn

2024

J. Chem. Theory Comput.

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Different electronic-structure methods were assessed for their ability to predict two important properties of the industrially relevant chelating agent nitrilotriacetic acid (NTA): its selectivity with respect to six different first-row transition metal ions and the spin-state energetics of its complex with Fe(III). The investigated methods encompassed density functional theory (DFT), the random phase approximation (RPA), coupled cluster (CC) theory, and the auxiliary-field quantum Monte Carlo (AFQMC) method, as well as the complete active space selfconsistent field (CASSCF) method and the respective on-top methods: second-order N-electron valence state perturbation theory (NEVPT2) and multiconfiguration pair-density functional theory (MC-PDFT). Different strategies for selecting active spaces were explored, and the density matrix renormalization group (DMRG) approach was used to solve the largest active spaces. Despite somewhat ambiguous multi-reference diagnostics, most methods gave relatively good agreement with experimental data for the chemical reactions connected to the selectivity, which only involved transition-metal complexes in their high-spin state. CC methods yielded the highest accuracy followed by range-separated DFT and AFQMC. We discussed in detail that even higher accuracies can be obtained with NEVPT2, under the prerequisite that consistent active spaces along the entire chemical reaction can be selected, which was not the case for reactions involving Fe(III). A bigger challenge for electronic-structure methods was the prediction of the spin-state energetics, which additionally involved lower spin states that exhibited larger multi-reference diagnostics. Conceptually different, typically accurate methods ranging from CC theory via DMRG-NEVPT2 in combination with large active spaces to AFQMC agreed well that the high-spin state is energetically significantly favored over the other spin states. This was in contrast to most DFT functionals and RPA which yielded a smaller stabilization and some common DFT functionals and MC-PDFT even predicting the low-spin state to be energetically most favorable.

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Experimental and Computational Insight into the Mechanism of NO Binding to Ferric Microperoxidase. The Likely Role of Tautomerization to Account for the pH Dependence

Cited by 12 publications

References 107 publications

Unraveling the Molecular Mechanism of S-Nitrosation Mediated by N-Acetylmicroperoxidase-11

Unraveling the Molecular Mechanism of S-Nitrosation Mediated by N-Acetylmicroperoxidase-11

A Personal Account on Inorganic Reaction Mechanisms

Chelate Complexes of 3d Transition Metal Ions─A Challenge for Electronic-Structure Methods?

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