A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion

There is recent evidence suggesting that nitrite anion (NO2 -) represents the major intravascular NO storage molecule whose transduction to NO is facilitated by a reduction mechanism catalyzed by deoxygenated hemoglobin (deoxy-Hb). In this work, we provide a detailed microscopic study of deoxy-Hb ni...

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Autores principales:	Perissinotti, Laura L., Martí, Marcelo Adrián, Doctorovich, Fabio Ariel, Estrin, Dario Ariel
Publicado:	2008
Materias:	Nitric oxide Deoxy hemoglobin Microscopic study Nitric oxides Nitrite anion Negative ions deoxyhemoglobin ferric ion heme histidine methemoglobin nitric oxide nitrite nitrite reductase nitrogen nitrous acid oxygen article catalysis complex formation enzyme activity human molecular dynamics priority journal proton transport quantum mechanics Anions Binding Sites Catalysis Hemoglobins Histidine Humans Ligands Models, Molecular Nitric Oxide Nitrite Reductases Nitrites Protein Conformation Bacteria (microorganisms)
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v47_n37_p9793_Perissinotti http://hdl.handle.net/20.500.12110/paper_00062960_v47_n37_p9793_Perissinotti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00062960_v47_n37_p9793_Perissinotti
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spelling	paper:paper_00062960_v47_n37_p9793_Perissinotti2023-06-08T14:30:43Z A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion Perissinotti, Laura L. Martí, Marcelo Adrián Doctorovich, Fabio Ariel Estrin, Dario Ariel Nitric oxide Deoxy hemoglobin Microscopic study Nitric oxides Nitrite anion Negative ions deoxyhemoglobin ferric ion heme histidine methemoglobin nitric oxide nitrite nitrite reductase nitrogen nitrous acid oxygen article catalysis complex formation enzyme activity human molecular dynamics priority journal proton transport quantum mechanics Anions Binding Sites Catalysis Hemoglobins Histidine Humans Ligands Models, Molecular Nitric Oxide Nitrite Reductases Nitrites Protein Conformation Bacteria (microorganisms) There is recent evidence suggesting that nitrite anion (NO2 -) represents the major intravascular NO storage molecule whose transduction to NO is facilitated by a reduction mechanism catalyzed by deoxygenated hemoglobin (deoxy-Hb). In this work, we provide a detailed microscopic study of deoxy-Hb nitrite reductase (NIR) activity by combining classical molecular dynamics and hybrid quantum mechanical-molecular mechanical simulations. Our results point out that two alternative mechanisms could be operative and suggest that the most energetic barriers should stem from either reprotonation of the distal histidine or NO dissociation from the ferric heme. In the first proposed mechanism, which is similar to that proposed for bacterial NIRs, nitrite anion or nitrous acid coordinates to the heme through the N atom. This pathway involves HisE7 in a one or two proton transfer process, depending on whether the active species is nitrite anion or nitrous acid, to yield an intermediate Fe(III)NO species which eventually dissociates leading to NO and methemoglobin. In the second mechanism, the nitrite anion coordinates to the heme through the O atom. This pathway requires only one proton transfer from HisE7 and leads directly to the formation of a hydroxo Fe(III) complex and NO. © 2008 American Chemical Society. Fil:Perissinotti, L.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Doctorovich, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v47_n37_p9793_Perissinotti http://hdl.handle.net/20.500.12110/paper_00062960_v47_n37_p9793_Perissinotti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Nitric oxide Deoxy hemoglobin Microscopic study Nitric oxides Nitrite anion Negative ions deoxyhemoglobin ferric ion heme histidine methemoglobin nitric oxide nitrite nitrite reductase nitrogen nitrous acid oxygen article catalysis complex formation enzyme activity human molecular dynamics priority journal proton transport quantum mechanics Anions Binding Sites Catalysis Hemoglobins Histidine Humans Ligands Models, Molecular Nitric Oxide Nitrite Reductases Nitrites Protein Conformation Bacteria (microorganisms)
spellingShingle	Nitric oxide Deoxy hemoglobin Microscopic study Nitric oxides Nitrite anion Negative ions deoxyhemoglobin ferric ion heme histidine methemoglobin nitric oxide nitrite nitrite reductase nitrogen nitrous acid oxygen article catalysis complex formation enzyme activity human molecular dynamics priority journal proton transport quantum mechanics Anions Binding Sites Catalysis Hemoglobins Histidine Humans Ligands Models, Molecular Nitric Oxide Nitrite Reductases Nitrites Protein Conformation Bacteria (microorganisms) Perissinotti, Laura L. Martí, Marcelo Adrián Doctorovich, Fabio Ariel Estrin, Dario Ariel A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
topic_facet	Nitric oxide Deoxy hemoglobin Microscopic study Nitric oxides Nitrite anion Negative ions deoxyhemoglobin ferric ion heme histidine methemoglobin nitric oxide nitrite nitrite reductase nitrogen nitrous acid oxygen article catalysis complex formation enzyme activity human molecular dynamics priority journal proton transport quantum mechanics Anions Binding Sites Catalysis Hemoglobins Histidine Humans Ligands Models, Molecular Nitric Oxide Nitrite Reductases Nitrites Protein Conformation Bacteria (microorganisms)
description	There is recent evidence suggesting that nitrite anion (NO2 -) represents the major intravascular NO storage molecule whose transduction to NO is facilitated by a reduction mechanism catalyzed by deoxygenated hemoglobin (deoxy-Hb). In this work, we provide a detailed microscopic study of deoxy-Hb nitrite reductase (NIR) activity by combining classical molecular dynamics and hybrid quantum mechanical-molecular mechanical simulations. Our results point out that two alternative mechanisms could be operative and suggest that the most energetic barriers should stem from either reprotonation of the distal histidine or NO dissociation from the ferric heme. In the first proposed mechanism, which is similar to that proposed for bacterial NIRs, nitrite anion or nitrous acid coordinates to the heme through the N atom. This pathway involves HisE7 in a one or two proton transfer process, depending on whether the active species is nitrite anion or nitrous acid, to yield an intermediate Fe(III)NO species which eventually dissociates leading to NO and methemoglobin. In the second mechanism, the nitrite anion coordinates to the heme through the O atom. This pathway requires only one proton transfer from HisE7 and leads directly to the formation of a hydroxo Fe(III) complex and NO. © 2008 American Chemical Society.
author	Perissinotti, Laura L. Martí, Marcelo Adrián Doctorovich, Fabio Ariel Estrin, Dario Ariel
author_facet	Perissinotti, Laura L. Martí, Marcelo Adrián Doctorovich, Fabio Ariel Estrin, Dario Ariel
author_sort	Perissinotti, Laura L.
title	A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
title_short	A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
title_full	A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
title_fullStr	A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
title_full_unstemmed	A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
title_sort	microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
publishDate	2008
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v47_n37_p9793_Perissinotti http://hdl.handle.net/20.500.12110/paper_00062960_v47_n37_p9793_Perissinotti
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A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion

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