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Bustamante, J.P.; Abbruzzetti, S.; Marcelli, A.; Gauto, D.; Boechi, L.; Bonamore, A.; Boffi, A.; Bruno, S.; Feis, A.; Foggi, P.; Estrin, D.A.; Viappiani, C. "Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins" (2014) Journal of Physical Chemistry B. 118(5):1234-1245
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Abstract:

Internal water molecules play an active role in ligand uptake regulation, since displacement of retained water molecules from protein surfaces or cavities by incoming ligands can promote favorable or disfavorable effects over the global binding process. Detection of these water molecules by X-ray crystallography is difficult given their positional disorder and low occupancy. In this work, we employ a combination of molecular dynamics simulations and ligand rebinding over a broad time range to shed light into the role of water molecules in ligand migration and binding. Computational studies on the unliganded structure of the thermostable truncated hemoglobin from Thermobifida fusca (Tf-trHbO) show that a water molecule is in the vicinity of the iron heme, stabilized by WG8 with the assistance of YCD1, exerting a steric hindrance for binding of an exogenous ligand. Mutation of WG8 to F results in a significantly lower stabilization of this water molecule and in subtle dynamical structural changes that favor ligand binding, as observed experimentally. Water is absent from the fully hydrophobic distal cavity of the triple mutant YB10F-YCD1F-WG8F (3F), due to the lack of residues capable of stabilizing it nearby the heme. In agreement with these effects on the barriers for ligand rebinding, over 97% of the photodissociated ligands are rebound within a few nanoseconds in the 3F mutant case. Our results demonstrate the specific involvement of water molecules in shaping the energetic barriers for ligand migration and binding. © 2014 American Chemical Society.

Registro:

Documento: Artículo
Título:Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins
Autor:Bustamante, J.P.; Abbruzzetti, S.; Marcelli, A.; Gauto, D.; Boechi, L.; Bonamore, A.; Boffi, A.; Bruno, S.; Feis, A.; Foggi, P.; Estrin, D.A.; Viappiani, C.
Filiación:Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Physics and Earth Sciences Macedonio Melloni, University of Parma, IBF-CNR, Parma, Italy
LENS, European Laboratory for Non-linear Spectroscopy, Florence, Italy
Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Istituto Pasteur, Department of Biochemical Sciences, University of Rome la Sapienza, Rome, Italy
Department of Pharmacy, University of Parma, Parma, Italy
Department of Chemistry Ugo Schiff, University of Florence, Florence, Italy
Department of Chemistry, University of Perugia, Perugia, Italy
INO-CNR, Florence, Italy
Palabras clave:Computational studies; Energetic barriers; Exogenous ligands; Hydrophobic cavities; Molecular dynamics simulations; Positional disorder; Thermobifida fusca; Truncated hemoglobins; Hemoglobin; Hydrophobicity; Molecular dynamics; Molecules; Porphyrins; X ray crystallography; Ligands; carbon monoxide; hemoglobin; ligand; truncated hemoglobin; water; article; chemical phenomena; chemistry; kinetics; metabolism; protein binding; protein tertiary structure; thermodynamics; Carbon Monoxide; Hemoglobins; Hydrophobic and Hydrophilic Interactions; Kinetics; Ligands; Protein Binding; Protein Structure, Tertiary; Thermodynamics; Truncated Hemoglobins; Water
Año:2014
Volumen:118
Número:5
Página de inicio:1234
Página de fin:1245
DOI: http://dx.doi.org/10.1021/jp410724z
Título revista:Journal of Physical Chemistry B
Título revista abreviado:J Phys Chem B
ISSN:15206106
CODEN:JPCBF
CAS:carbon monoxide, 630-08-0; hemoglobin, 9008-02-0; water, 7732-18-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v118_n5_p1234_Bustamante

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Citas:

---------- APA ----------
Bustamante, J.P., Abbruzzetti, S., Marcelli, A., Gauto, D., Boechi, L., Bonamore, A., Boffi, A.,..., Viappiani, C. (2014) . Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins. Journal of Physical Chemistry B, 118(5), 1234-1245.
http://dx.doi.org/10.1021/jp410724z
---------- CHICAGO ----------
Bustamante, J.P., Abbruzzetti, S., Marcelli, A., Gauto, D., Boechi, L., Bonamore, A., et al. "Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins" . Journal of Physical Chemistry B 118, no. 5 (2014) : 1234-1245.
http://dx.doi.org/10.1021/jp410724z
---------- MLA ----------
Bustamante, J.P., Abbruzzetti, S., Marcelli, A., Gauto, D., Boechi, L., Bonamore, A., et al. "Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins" . Journal of Physical Chemistry B, vol. 118, no. 5, 2014, pp. 1234-1245.
http://dx.doi.org/10.1021/jp410724z
---------- VANCOUVER ----------
Bustamante, J.P., Abbruzzetti, S., Marcelli, A., Gauto, D., Boechi, L., Bonamore, A., et al. Ligand uptake modulation by internal water molecules and hydrophobic cavities in hemoglobins. J Phys Chem B. 2014;118(5):1234-1245.
http://dx.doi.org/10.1021/jp410724z