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Abstract:

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.

Registro:

Documento: Artículo
Título:A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion
Autor:Perissinotti, L.L.; Marti, M.A.; Doctorovich, F.; Luque, F.J.; Estrin, D.A.
Filiación:Departamento de Quimica Inorganica, Analitica Y Quimica Fisica/INQUIMAE, Facultad de Ciencias Exactas Y Naturales, Pabellón II, C1428EHA Buenos Aires, Argentina
Departament de Fisicoquímica, Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain
Palabras clave: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)
Año:2008
Volumen:47
Número:37
Página de inicio:9793
Página de fin:9802
DOI: http://dx.doi.org/10.1021/bi801104c
Título revista:Biochemistry
Título revista abreviado:Biochemistry
ISSN:00062960
CODEN:BICHA
CAS:ferric ion, 20074-52-6; heme, 14875-96-8; histidine, 645-35-2, 7006-35-1, 71-00-1; nitric oxide, 10102-43-9; nitrite reductase, 9080-03-9; nitrite, 14797-65-0; nitrogen, 7727-37-9; nitrous acid, 7782-77-6; oxygen, 7782-44-7; Anions; deoxyhemoglobin, 9008-02-0; Hemoglobins; Histidine, 71-00-1; Ligands; Nitric Oxide, 10102-43-9; Nitrite Reductases, EC 1.7.-; Nitrites
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v47_n37_p9793_Perissinotti

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Citas:

---------- APA ----------
Perissinotti, L.L., Marti, M.A., Doctorovich, F., Luque, F.J. & Estrin, D.A. (2008) . A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion. Biochemistry, 47(37), 9793-9802.
http://dx.doi.org/10.1021/bi801104c
---------- CHICAGO ----------
Perissinotti, L.L., Marti, M.A., Doctorovich, F., Luque, F.J., Estrin, D.A. "A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion" . Biochemistry 47, no. 37 (2008) : 9793-9802.
http://dx.doi.org/10.1021/bi801104c
---------- MLA ----------
Perissinotti, L.L., Marti, M.A., Doctorovich, F., Luque, F.J., Estrin, D.A. "A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion" . Biochemistry, vol. 47, no. 37, 2008, pp. 9793-9802.
http://dx.doi.org/10.1021/bi801104c
---------- VANCOUVER ----------
Perissinotti, L.L., Marti, M.A., Doctorovich, F., Luque, F.J., Estrin, D.A. A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide from nitrite anion. Biochemistry. 2008;47(37):9793-9802.
http://dx.doi.org/10.1021/bi801104c