title: Simulation of catalytic water activation in mitochondrial F1-ATPase using a hybrid quantum mechanics/molecular mechanics approach: an alternative role for β-Glu 188.
abstract: The use of quantum mechanics/molecular mechanics simulations to study the free energy landscape of the water activation at the catalytic site of mitochondrial F(1)-ATPase affords us insight into the generation of the nucleophile OH(-) prior to ATP hydrolysis. As a result, the ATP molecule was found to be the final proton acceptor. In the simulated pathway, the transfer of a proton to the nucleotide was not direct but occurred via a second water molecule in a manner similar to the Grotthuss mechanism proposed for proton diffusion. Residue β-Glu 188, previously described as the putative catalytic base, was found to be involved in the stabilization of a transient hydronium ion during water activation. Simulations in the absence of the carboxylate moiety of β-Glu 188 support this role.
authors: Molecular Modelling Group, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera 1, Cantoblanco, Madrid, Spain.
authors: Fernando
authors: F
authors: Martín-García
authors: Jesús I
authors: JI
authors: Mendieta-Moreno
authors: Iñigo
authors: I
authors: Marcos-Alcalde
authors: Paulino
authors: P
authors: Gómez-Puertas
authors: Jesús
authors: J
authors: Mendieta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*; D011522:Protons; D011789:Quantum Theory; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011522:Protons; D014867:Water; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases