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Abstract:

Myoglobin (Mb) and hemoglobin have the biological ability to carry/store oxygen (O2), a property which requires its heme iron atom to be in the ferrous -Fe(II)- state. However, the thermodynamically stable state in the presence of O2 is Fe(III) and thus the oxidation rate of a globin is a critical parameter related to its function. Mb has been extensively studied and many mutants have been characterized regarding its oxygen mediated oxidation (i.e., autoxidation) rates. Site directed mutants in residues 29 (B10), which shapes the distal cavity, and 64 (E7), the well-known histidine gate, have been shown to display a wide range of autoxidation rate constants. In this work, we have thoroughly studied the mechanism underlying the autoxidation process by means of state-of-the-art computer simulation methodologies, using Mb and site directed mutants as benchmark cases. Our results explain the observed autoxidation rate tendencies in different variants of Mb, L29F < wt < L29A = H64Q < H64F < H64A, and shed light on several aspects of the reaction at the atomic level. First, water access to the distal pocket is a key event and the observed acid catalysis relies on HisE7 protonation and opening of the His gate to allow water access, rather than protonation of the oxy heme itself. Our results also suggest that the basic mechanism, i.e., superoxide displacement by hydroxide anion, is energetically more feasible. Finally, we confirmed that distal hydrogen bonds protect the oxy complex from autoxidation. © 2015 American Chemical Society.

Registro:

Documento: Artículo
Título:Molecular mechanism of myoglobin autoxidation: Insights from computer simulations
Autor:Arcon, J.P.; Rosi, P.; Petruk, A.A.; Marti, M.A.; Estrin, D.A.
Filiación:Departamento de Quimica Inorganica, Analitica y Quimica Fisica e INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina
Palabras clave:Amino acids; Hemoglobin; Hydrogen bonds; Iron compounds; Oxygen; Porphyrins; Protonation; Rate constants; Acid catalysis; Basic mechanism; Hydroxide anions; Molecular mechanism; Oxidation rates; Simulation methodology; State of the art; Thermodynamically stable; Oxidation; heme; myoglobin; oxygen; catalysis; chemistry; computer simulation; genetics; hydrogen bond; metabolism; molecular dynamics; mutation; oxidation reduction reaction; quantum theory; thermodynamics; Catalysis; Computer Simulation; Heme; Hydrogen Bonding; Molecular Dynamics Simulation; Mutation; Myoglobin; Oxidation-Reduction; Oxygen; Quantum Theory; Thermodynamics
Año:2015
Volumen:119
Número:5
Página de inicio:1802
Página de fin:1813
DOI: http://dx.doi.org/10.1021/jp5093948
Título revista:Journal of Physical Chemistry A
Título revista abreviado:J Phys Chem A
ISSN:10895639
CODEN:JPCAF
CAS:heme, 14875-96-8; oxygen, 7782-44-7; Heme; Myoglobin; Oxygen
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10895639_v119_n5_p1802_Arcon

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Citas:

---------- APA ----------
Arcon, J.P., Rosi, P., Petruk, A.A., Marti, M.A. & Estrin, D.A. (2015) . Molecular mechanism of myoglobin autoxidation: Insights from computer simulations. Journal of Physical Chemistry A, 119(5), 1802-1813.
http://dx.doi.org/10.1021/jp5093948
---------- CHICAGO ----------
Arcon, J.P., Rosi, P., Petruk, A.A., Marti, M.A., Estrin, D.A. "Molecular mechanism of myoglobin autoxidation: Insights from computer simulations" . Journal of Physical Chemistry A 119, no. 5 (2015) : 1802-1813.
http://dx.doi.org/10.1021/jp5093948
---------- MLA ----------
Arcon, J.P., Rosi, P., Petruk, A.A., Marti, M.A., Estrin, D.A. "Molecular mechanism of myoglobin autoxidation: Insights from computer simulations" . Journal of Physical Chemistry A, vol. 119, no. 5, 2015, pp. 1802-1813.
http://dx.doi.org/10.1021/jp5093948
---------- VANCOUVER ----------
Arcon, J.P., Rosi, P., Petruk, A.A., Marti, M.A., Estrin, D.A. Molecular mechanism of myoglobin autoxidation: Insights from computer simulations. J Phys Chem A. 2015;119(5):1802-1813.
http://dx.doi.org/10.1021/jp5093948