Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7
Since the elucidation of the myoglobin (Mb) structure, a histidine residue on the E helix (His-E7) has been proposed to act as a gate with an open or closed conformation controlling access to the active site. Although it is believed that at low pH, the His-E7 gate is in its open conformation, the fu...
Guardado en:
| Autores principales: | , , |
|---|---|
| Publicado: |
2013
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v288_n9_p6754_Boechi http://hdl.handle.net/20.500.12110/paper_00219258_v288_n9_p6754_Boechi |
| Aporte de: |
| id |
paper:paper_00219258_v288_n9_p6754_Boechi |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_00219258_v288_n9_p6754_Boechi2023-06-08T14:43:35Z Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel Active site Conceptual frameworks Energy profile Histidine residues Hydrophobic effect Hydrophobic sites Molecular dynamics simulations Open conformation Oxygen migration Oxygen uptake Protonation state Rate enhancement Side-chains Significant differences Amino acids Hydrophobicity Ligands Molecular dynamics Oxygen Protonation Conformations alanine histidine histidine E7 myoglobin oxygen tryptophan unclassified drug article chemical structure energy transfer hydrophobicity molecular dynamics oxygen consumption oxygen transport priority journal protein conformation proton transport Animals Histidine Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Myoglobin Oxygen Protein Binding Protein Structure, Secondary Since the elucidation of the myoglobin (Mb) structure, a histidine residue on the E helix (His-E7) has been proposed to act as a gate with an open or closed conformation controlling access to the active site. Although it is believed that at low pH, the His-E7 gate is in its open conformation, the full relationship between the His-E7 protonation state, its conformation, and ligand migration in Mb is hotly debated. We used molecular dynamics simulations to first address the effect of His-E7 protonation on its conformation. We observed the expected shift from the closed to the open conformation upon protonation, but more importantly, noted a significant difference between the conformations of the two neutral histidine tautomers. We further computed free energy profiles for oxygen migration in each of the possible His-E7 states as well as in two instructive Mb mutants: Ala-E7 and Trp-E7. Our results show that even in the closed conformation, the His-E7 gate does not create a large barrier to oxygen migration and permits oxygen entry with only a small rotation of the imidazole side chain and movement of the E helix. We identify, instead, a hydrophobic site in the E7 channel that can accommodate an apolar diatomic ligand and enhances ligand uptake particularly in the open His-E7 conformation. This rate enhancement is diminished in the closed conformation. Taken together, our results provide a new conceptual framework for the histidine gate hypothesis. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Fil:Boechi, L. 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. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v288_n9_p6754_Boechi http://hdl.handle.net/20.500.12110/paper_00219258_v288_n9_p6754_Boechi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Active site Conceptual frameworks Energy profile Histidine residues Hydrophobic effect Hydrophobic sites Molecular dynamics simulations Open conformation Oxygen migration Oxygen uptake Protonation state Rate enhancement Side-chains Significant differences Amino acids Hydrophobicity Ligands Molecular dynamics Oxygen Protonation Conformations alanine histidine histidine E7 myoglobin oxygen tryptophan unclassified drug article chemical structure energy transfer hydrophobicity molecular dynamics oxygen consumption oxygen transport priority journal protein conformation proton transport Animals Histidine Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Myoglobin Oxygen Protein Binding Protein Structure, Secondary |
| spellingShingle |
Active site Conceptual frameworks Energy profile Histidine residues Hydrophobic effect Hydrophobic sites Molecular dynamics simulations Open conformation Oxygen migration Oxygen uptake Protonation state Rate enhancement Side-chains Significant differences Amino acids Hydrophobicity Ligands Molecular dynamics Oxygen Protonation Conformations alanine histidine histidine E7 myoglobin oxygen tryptophan unclassified drug article chemical structure energy transfer hydrophobicity molecular dynamics oxygen consumption oxygen transport priority journal protein conformation proton transport Animals Histidine Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Myoglobin Oxygen Protein Binding Protein Structure, Secondary Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| topic_facet |
Active site Conceptual frameworks Energy profile Histidine residues Hydrophobic effect Hydrophobic sites Molecular dynamics simulations Open conformation Oxygen migration Oxygen uptake Protonation state Rate enhancement Side-chains Significant differences Amino acids Hydrophobicity Ligands Molecular dynamics Oxygen Protonation Conformations alanine histidine histidine E7 myoglobin oxygen tryptophan unclassified drug article chemical structure energy transfer hydrophobicity molecular dynamics oxygen consumption oxygen transport priority journal protein conformation proton transport Animals Histidine Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Myoglobin Oxygen Protein Binding Protein Structure, Secondary |
| description |
Since the elucidation of the myoglobin (Mb) structure, a histidine residue on the E helix (His-E7) has been proposed to act as a gate with an open or closed conformation controlling access to the active site. Although it is believed that at low pH, the His-E7 gate is in its open conformation, the full relationship between the His-E7 protonation state, its conformation, and ligand migration in Mb is hotly debated. We used molecular dynamics simulations to first address the effect of His-E7 protonation on its conformation. We observed the expected shift from the closed to the open conformation upon protonation, but more importantly, noted a significant difference between the conformations of the two neutral histidine tautomers. We further computed free energy profiles for oxygen migration in each of the possible His-E7 states as well as in two instructive Mb mutants: Ala-E7 and Trp-E7. Our results show that even in the closed conformation, the His-E7 gate does not create a large barrier to oxygen migration and permits oxygen entry with only a small rotation of the imidazole side chain and movement of the E helix. We identify, instead, a hydrophobic site in the E7 channel that can accommodate an apolar diatomic ligand and enhances ligand uptake particularly in the open His-E7 conformation. This rate enhancement is diminished in the closed conformation. Taken together, our results provide a new conceptual framework for the histidine gate hypothesis. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. |
| author |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Boechi, Leonardo |
| title |
Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| title_short |
Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| title_full |
Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| title_fullStr |
Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| title_full_unstemmed |
Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7 |
| title_sort |
hydrophobic effect drives oxygen uptake in myoglobin via histidine e7 |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v288_n9_p6754_Boechi http://hdl.handle.net/20.500.12110/paper_00219258_v288_n9_p6754_Boechi |
| work_keys_str_mv |
AT boechileonardo hydrophobiceffectdrivesoxygenuptakeinmyoglobinviahistidinee7 AT martimarceloadrian hydrophobiceffectdrivesoxygenuptakeinmyoglobinviahistidinee7 AT estrindarioariel hydrophobiceffectdrivesoxygenuptakeinmyoglobinviahistidinee7 |
| _version_ |
1768543166422581248 |