Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra
Human hemoglobin (Hb) Coimbra (βAsp99Glu) is one of the seven βAsp99 Hb variants described to date. All βAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since βA...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v637_n_p73_Jorge http://hdl.handle.net/20.500.12110/paper_00039861_v637_n_p73_Jorge |
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paper:paper_00039861_v637_n_p73_Jorge2023-06-08T14:25:06Z Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra Allostery Hb Coimbra Hemoglobin variant Oxygen affinity Polycythemia hemoglobin coimbra hemoglobin hotel dieu hemoglobin kempsey hemoglobin radcliffe hemoglobin variant hemoglobin yakima hemoglobin ypsilanti oxygen phytic acid unclassified drug 2,3 diphosphoglyceric acid heme hemoglobin Coimbra hemoglobin variant oxygen phytic acid allosterism Article blood viscosity computer simulation conformational transition controlled study dissociation rate constant erythrocytosis hemolysate human hypoxemia molecular dynamics molecular probe oximetry oxygen affinity priority journal protein function protein modification chemistry genetics in vitro study kinetics metabolism molecular model protein domain protein quaternary structure 2,3-Diphosphoglycerate Allosteric Regulation Heme Hemoglobins, Abnormal Humans In Vitro Techniques Kinetics Models, Molecular Molecular Dynamics Simulation Oxygen Phytic Acid Protein Interaction Domains and Motifs Protein Structure, Quaternary Human hemoglobin (Hb) Coimbra (βAsp99Glu) is one of the seven βAsp99 Hb variants described to date. All βAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since βAsp99 plays an important role in the allosteric α1β2 interface and the mutation in Hb Coimbra only represents the insertion of a CH2 group in this interface, the present study of Hb Coimbra is important for a better understanding of the global impact of small modifications in this allosteric interface. We carried out functional, kinetic and dynamic characterization of this hemoglobin, focusing on the interpretation of these results in the context of a growth of the position 99 side chain length in the α1β2 interface. Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr effect), and the heme-heme cooperativity was analyzed by determining the Hill coefficient (n), in addition to the effect of the allosteric effectors inositol hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer simulations revealed a stabilization of the R state in the Coimbra variant with respect to the wild type, and consistently, the T-to-R quaternary transition was observed on the nanosecond time scale of classical molecular dynamics simulations. © 2017 Elsevier Inc. 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v637_n_p73_Jorge http://hdl.handle.net/20.500.12110/paper_00039861_v637_n_p73_Jorge |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Allostery Hb Coimbra Hemoglobin variant Oxygen affinity Polycythemia hemoglobin coimbra hemoglobin hotel dieu hemoglobin kempsey hemoglobin radcliffe hemoglobin variant hemoglobin yakima hemoglobin ypsilanti oxygen phytic acid unclassified drug 2,3 diphosphoglyceric acid heme hemoglobin Coimbra hemoglobin variant oxygen phytic acid allosterism Article blood viscosity computer simulation conformational transition controlled study dissociation rate constant erythrocytosis hemolysate human hypoxemia molecular dynamics molecular probe oximetry oxygen affinity priority journal protein function protein modification chemistry genetics in vitro study kinetics metabolism molecular model protein domain protein quaternary structure 2,3-Diphosphoglycerate Allosteric Regulation Heme Hemoglobins, Abnormal Humans In Vitro Techniques Kinetics Models, Molecular Molecular Dynamics Simulation Oxygen Phytic Acid Protein Interaction Domains and Motifs Protein Structure, Quaternary |
| spellingShingle |
Allostery Hb Coimbra Hemoglobin variant Oxygen affinity Polycythemia hemoglobin coimbra hemoglobin hotel dieu hemoglobin kempsey hemoglobin radcliffe hemoglobin variant hemoglobin yakima hemoglobin ypsilanti oxygen phytic acid unclassified drug 2,3 diphosphoglyceric acid heme hemoglobin Coimbra hemoglobin variant oxygen phytic acid allosterism Article blood viscosity computer simulation conformational transition controlled study dissociation rate constant erythrocytosis hemolysate human hypoxemia molecular dynamics molecular probe oximetry oxygen affinity priority journal protein function protein modification chemistry genetics in vitro study kinetics metabolism molecular model protein domain protein quaternary structure 2,3-Diphosphoglycerate Allosteric Regulation Heme Hemoglobins, Abnormal Humans In Vitro Techniques Kinetics Models, Molecular Molecular Dynamics Simulation Oxygen Phytic Acid Protein Interaction Domains and Motifs Protein Structure, Quaternary Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| topic_facet |
Allostery Hb Coimbra Hemoglobin variant Oxygen affinity Polycythemia hemoglobin coimbra hemoglobin hotel dieu hemoglobin kempsey hemoglobin radcliffe hemoglobin variant hemoglobin yakima hemoglobin ypsilanti oxygen phytic acid unclassified drug 2,3 diphosphoglyceric acid heme hemoglobin Coimbra hemoglobin variant oxygen phytic acid allosterism Article blood viscosity computer simulation conformational transition controlled study dissociation rate constant erythrocytosis hemolysate human hypoxemia molecular dynamics molecular probe oximetry oxygen affinity priority journal protein function protein modification chemistry genetics in vitro study kinetics metabolism molecular model protein domain protein quaternary structure 2,3-Diphosphoglycerate Allosteric Regulation Heme Hemoglobins, Abnormal Humans In Vitro Techniques Kinetics Models, Molecular Molecular Dynamics Simulation Oxygen Phytic Acid Protein Interaction Domains and Motifs Protein Structure, Quaternary |
| description |
Human hemoglobin (Hb) Coimbra (βAsp99Glu) is one of the seven βAsp99 Hb variants described to date. All βAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since βAsp99 plays an important role in the allosteric α1β2 interface and the mutation in Hb Coimbra only represents the insertion of a CH2 group in this interface, the present study of Hb Coimbra is important for a better understanding of the global impact of small modifications in this allosteric interface. We carried out functional, kinetic and dynamic characterization of this hemoglobin, focusing on the interpretation of these results in the context of a growth of the position 99 side chain length in the α1β2 interface. Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr effect), and the heme-heme cooperativity was analyzed by determining the Hill coefficient (n), in addition to the effect of the allosteric effectors inositol hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer simulations revealed a stabilization of the R state in the Coimbra variant with respect to the wild type, and consistently, the T-to-R quaternary transition was observed on the nanosecond time scale of classical molecular dynamics simulations. © 2017 Elsevier Inc. |
| title |
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| title_short |
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| title_full |
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| title_fullStr |
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| title_full_unstemmed |
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra |
| title_sort |
understanding the molecular basis of the high oxygen affinity variant human hemoglobin coimbra |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v637_n_p73_Jorge http://hdl.handle.net/20.500.12110/paper_00039861_v637_n_p73_Jorge |
| _version_ |
1768544573991157760 |