Nadra, A.D.; Martí, M.A.; Pesce, A.; Bolognesi, M.; Estrin, D.A. "Exploring the molecular basis of heme coordination in human neuroglobin" (2008) Proteins: Structure, Function and Genetics. 71(2):695-705
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Neuroglobin (Ngb), a recently discovered ancient heme protein, presents the typical globin fold and is around 20% identical to myoglobin (Mb). In contrast with Mb, however, its heme is hexacoordinated (6c). It is expressed in the nervous system and has been the subject of numerous investigations in the last years, but its function is still unclear. The proposed roles include oxygen transport, reactive oxygen species (ROS) detoxification, hypoxia protection, and redox state sensing. All proposed functions require distal histidine dissociation from the heme to yield a reactive iron. With the aim of understanding the 6c to 5c transition, we have performed molecular dynamics simulations for ferrous Ngb in the 6c, 5c, and oxy states. We also computed free energy profiles associated with the transition employing an advanced sampling technique. Finally, we studied the effect of the redox state of CysCD7 and CysD5, which are known to form a disulfide bridge. Our results show that protein oxidation promotes a stabilization of the pentacoordinated species, thus favoring the protein to adopt the more reactive state and supporting the existence of a molecular mechanism whereby O2 would be released under hypoxic conditions, thereby suggesting an O2 storage function for Ngb. Taken together, our results provide structural information not available experimentally which may shed light on the protein proposed functions, particularly as a redox sensor. © 2007 Wiley-Liss, Inc.


Documento: Artículo
Título:Exploring the molecular basis of heme coordination in human neuroglobin
Autor:Nadra, A.D.; Martí, M.A.; Pesce, A.; Bolognesi, M.; Estrin, D.A.
Filiación:Departamento de Quimica Inorganica, Analitica Y Quimica Fisica/INQUIMAE-CONICET, Facultad de Ciencias Exactas Y Naturales, Pabellón II, Buenos Aires (C1428EHA), Argentina
Department of Physics, Center of Excellence for Biomedical Research, University of Genova, 16136, Genova, Italy
Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, I-20131 Milano, Italy
Palabras clave:Globin; Heme protein; Hexacoordination; Molecular dynamics; Neuroglobin; cysteine; disulfide; heme; hemoprotein; histidine; iron; myoglobin; neuroglobin; oxygen; protein; reactive oxygen metabolite; article; comparative study; detoxification; hypoxia; kinetics; molecular biology; molecular dynamics; molecular stability; oxidation reduction reaction; oxidation reduction state; oxygen transport; priority journal; protein analysis; protein expression; protein structure; sampling; sensor; Animals; Computer Simulation; Crystallography, X-Ray; Globins; Heme; Histidine; Humans; Ligands; Mice; Models, Molecular; Nerve Tissue Proteins; Protein Binding; Protein Conformation; Thermodynamics
Página de inicio:695
Página de fin:705
Título revista:Proteins: Structure, Function and Genetics
Título revista abreviado:Proteins Struct. Funct. Genet.
CAS:cysteine, 4371-52-2, 52-89-1, 52-90-4; disulfide, 16734-12-6; heme, 14875-96-8; histidine, 645-35-2, 7006-35-1, 71-00-1; iron, 14093-02-8, 53858-86-9, 7439-89-6; oxygen, 7782-44-7; protein, 67254-75-5; Globins, 9004-22-2; Heme, 14875-96-8; Histidine, 71-00-1; Ligands; Nerve Tissue Proteins; neuroglobin


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---------- APA ----------
Nadra, A.D., Martí, M.A., Pesce, A., Bolognesi, M. & Estrin, D.A. (2008) . Exploring the molecular basis of heme coordination in human neuroglobin. Proteins: Structure, Function and Genetics, 71(2), 695-705.
---------- CHICAGO ----------
Nadra, A.D., Martí, M.A., Pesce, A., Bolognesi, M., Estrin, D.A. "Exploring the molecular basis of heme coordination in human neuroglobin" . Proteins: Structure, Function and Genetics 71, no. 2 (2008) : 695-705.
---------- MLA ----------
Nadra, A.D., Martí, M.A., Pesce, A., Bolognesi, M., Estrin, D.A. "Exploring the molecular basis of heme coordination in human neuroglobin" . Proteins: Structure, Function and Genetics, vol. 71, no. 2, 2008, pp. 695-705.
---------- VANCOUVER ----------
Nadra, A.D., Martí, M.A., Pesce, A., Bolognesi, M., Estrin, D.A. Exploring the molecular basis of heme coordination in human neuroglobin. Proteins Struct. Funct. Genet. 2008;71(2):695-705.