In this paper, by using the perturbed matrix method (PMM) in combination with basic statistical mechanical relations both based on nanosecond time-scale molecular dynamics (MD) simulations, we quantitatively address the thermodynamics of compound 0 (Cpd 0) formation in horseradish peroxidase (HRP) enzyme. Our results, in the same trend of low-temperature experimental data, obtained in cryoenzymology studies indicate that such a reaction can be described essentially as a stepwise spontaneous process: a first step mechanically constrained, strongly exothermic proton transfer from the heme-H2O2 complex to the conserved His42, followed by a solvent-protein relaxation involving a large entropy increase. Critical evaluation of PMM/MD data also reveals the crucial role played by specific residues in the reaction pocket and, more in general, by the conformational fluctuations of the overall environment in physiological conditions.

Zazza, C., Amadei, A., Palma, A., Sanna, N., Tatoli, S., Aschi, M. (2008). Theoretical modeling of enzyme reactions: The thermodynamics of formation of compound 0 in horseradish peroxidase. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 112(10), 3184-3192 [10.1021/jp0774692].

Theoretical modeling of enzyme reactions: The thermodynamics of formation of compound 0 in horseradish peroxidase

AMADEI, ANDREA;
2008-01-01

Abstract

In this paper, by using the perturbed matrix method (PMM) in combination with basic statistical mechanical relations both based on nanosecond time-scale molecular dynamics (MD) simulations, we quantitatively address the thermodynamics of compound 0 (Cpd 0) formation in horseradish peroxidase (HRP) enzyme. Our results, in the same trend of low-temperature experimental data, obtained in cryoenzymology studies indicate that such a reaction can be described essentially as a stepwise spontaneous process: a first step mechanically constrained, strongly exothermic proton transfer from the heme-H2O2 complex to the conserved His42, followed by a solvent-protein relaxation involving a large entropy increase. Critical evaluation of PMM/MD data also reveals the crucial role played by specific residues in the reaction pocket and, more in general, by the conformational fluctuations of the overall environment in physiological conditions.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore CHIM/02 - Chimica Fisica
English
Con Impact Factor ISI
Addition reactions; Enzymes; Food additives; Molecular dynamics; Porphyrins; Proton transfer; Quantum chemistry; Reaction kinetics; Thermodynamics; (e ,3e) process; Enzyme reactions; Experimental data; Horse radish peroxidase (HRP); Horseradish peroxidase (HRP) enzyme; Molecular-dynamics (MD) simulations; Perturbed matrix method (PMM); time scaling; Dynamics; horseradish peroxidase; article; biological model; chemical structure; chemistry; computer simulation; metabolism; thermodynamics; Computer Simulation; Horseradish Peroxidase; Models, Biological; Models, Molecular; Molecular Structure; Thermodynamics
Zazza, C., Amadei, A., Palma, A., Sanna, N., Tatoli, S., Aschi, M. (2008). Theoretical modeling of enzyme reactions: The thermodynamics of formation of compound 0 in horseradish peroxidase. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 112(10), 3184-3192 [10.1021/jp0774692].
Zazza, C; Amadei, A; Palma, A; Sanna, N; Tatoli, S; Aschi, M
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/23569
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