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Abstract:

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.

Registro:

Documento: Artículo
Título:Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7
Autor:Boechi, L.; Arrar, M.; Martí, M.A.; Olson, J.S.; Roitberg, A.E.; Estrin, D.A.
Filiación:Departamento de Quimica Inorganica, Analitica, y Quimica Fisica/Inquimae-Conicet, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, C1428EHA Buenos Aires, Argentina
Department of Chemistry and Quantum Theory Project, University of Florida, PO BOX 117200, Gainesville, FL 32611-7022, United States
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, C1428EHA Buenos Aires, Argentina
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005-1892, United States
Dept. of Chemistry and Biochemistry, University of California, San Diego, CA 92093-0365, United States
Palabras clave: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
Año:2013
Volumen:288
Número:9
Página de inicio:6754
Página de fin:6762
DOI: http://dx.doi.org/10.1074/jbc.M112.426056
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:alanine, 56-41-7, 6898-94-8; histidine, 645-35-2, 7006-35-1, 71-00-1; oxygen, 7782-44-7; tryptophan, 6912-86-3, 73-22-3; Histidine, 71-00-1; Myoglobin; Oxygen, 7782-44-7
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v288_n9_p6754_Boechi.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v288_n9_p6754_Boechi

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Citas:

---------- APA ----------
Boechi, L., Arrar, M., Martí, M.A., Olson, J.S., Roitberg, A.E. & Estrin, D.A. (2013) . Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7. Journal of Biological Chemistry, 288(9), 6754-6762.
http://dx.doi.org/10.1074/jbc.M112.426056
---------- CHICAGO ----------
Boechi, L., Arrar, M., Martí, M.A., Olson, J.S., Roitberg, A.E., Estrin, D.A. "Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7" . Journal of Biological Chemistry 288, no. 9 (2013) : 6754-6762.
http://dx.doi.org/10.1074/jbc.M112.426056
---------- MLA ----------
Boechi, L., Arrar, M., Martí, M.A., Olson, J.S., Roitberg, A.E., Estrin, D.A. "Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7" . Journal of Biological Chemistry, vol. 288, no. 9, 2013, pp. 6754-6762.
http://dx.doi.org/10.1074/jbc.M112.426056
---------- VANCOUVER ----------
Boechi, L., Arrar, M., Martí, M.A., Olson, J.S., Roitberg, A.E., Estrin, D.A. Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7. J. Biol. Chem. 2013;288(9):6754-6762.
http://dx.doi.org/10.1074/jbc.M112.426056