Exploring the molecular basis of heme coordination in human neuroglobin
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...
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2008
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v71_n2_p695_Nadra http://hdl.handle.net/20.500.12110/paper_08873585_v71_n2_p695_Nadra |
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paper:paper_08873585_v71_n2_p695_Nadra2023-06-08T15:46:47Z Exploring the molecular basis of heme coordination in human neuroglobin Nadra, Alejandro Daniel Martí, Marcelo Adrián Estrin, Dario Ariel 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 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. Fil:Nadra, A.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martí, M.A. 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_08873585_v71_n2_p695_Nadra http://hdl.handle.net/20.500.12110/paper_08873585_v71_n2_p695_Nadra |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Nadra, Alejandro Daniel Martí, Marcelo Adrián Estrin, Dario Ariel Exploring the molecular basis of heme coordination in human neuroglobin |
| topic_facet |
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 |
| description |
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. |
| author |
Nadra, Alejandro Daniel Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Nadra, Alejandro Daniel Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Nadra, Alejandro Daniel |
| title |
Exploring the molecular basis of heme coordination in human neuroglobin |
| title_short |
Exploring the molecular basis of heme coordination in human neuroglobin |
| title_full |
Exploring the molecular basis of heme coordination in human neuroglobin |
| title_fullStr |
Exploring the molecular basis of heme coordination in human neuroglobin |
| title_full_unstemmed |
Exploring the molecular basis of heme coordination in human neuroglobin |
| title_sort |
exploring the molecular basis of heme coordination in human neuroglobin |
| publishDate |
2008 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v71_n2_p695_Nadra http://hdl.handle.net/20.500.12110/paper_08873585_v71_n2_p695_Nadra |
| work_keys_str_mv |
AT nadraalejandrodaniel exploringthemolecularbasisofhemecoordinationinhumanneuroglobin AT martimarceloadrian exploringthemolecularbasisofhemecoordinationinhumanneuroglobin AT estrindarioariel exploringthemolecularbasisofhemecoordinationinhumanneuroglobin |
| _version_ |
1768542418826690560 |