Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7

En:

J. Biol. Chem. 2013;288(9):6754-6762

Fecha:

2013

Formato:

application/pdf

Tipo de documento:

info:eu-repo/semantics/article
info:ar-repo/semantics/artículo
info:eu-repo/semantics/publishedVersion

Descriptores:

Active site -  Conceptual frameworks -  Energy profile -  Histidine residues -  Hydrophobic effect -  Hydrophobic sites -  Molecular dynamics simulations -  Open conformation -  Oxygen migration

Descripción:

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.

Identificador(es):

http://hdl.handle.net/20.500.12110/paper_00219258_v288_n9_p6754_Boechi

Derechos:

info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.5/ar