Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/96349
Author(s): Daniel F A R Dourado
Pedro Alexandrino Fernandes
Bengt Mannervik
Maria Joao Ramos
Title: Glutathione Transferase A1-1: Catalytic Importance of Arginine 15
Issue Date: 2010
Abstract: Glutathione transferases (GSTs) are fundamental enzymes of the cell detoxification system. They catalyze the nucleophilic attack Of glutathione (GSH) on electrophilic substrates to produce less toxic compounds. The resulting Substrate can then be recognized by ATP-dependent transmembrane PUMPS and consequently expelled from the cell. Despite all the existing studies on GSTs, many aspects of the catalytic events are still poorly understood. Recently, using as a model the GSTAI-1 enzyme, we proposed it GSH activation mechanism. Resorting to the density functional theory (DFT), we demonstrated that a water molecule could assist a proton transfer between (lie GSH thiol and (x-carboxylic groups. after all initial conformational rearrangement of GSH, as evidenced by potential of mean force calculations. In this work to elucidate the catalytic role of Arg 15, a strictly conserved active site residue in class alpha GSTs. we analyzed the activation energy barrier and Structural details associated with the GSTAI-1 Mutants R15A, R15R epsilon, eta-c (an Arg residue with the epsilon-eta-nitrogens Substituted by carbons), and R 15Rneutral (a neutral Arg residue due to the a addition of a hydride in the zeta-carbon. A similar mechanism to the one used in Our GSH activation proposal was implemented.
Subject: Química
Chemical sciences
Scientific areas: Ciências exactas e naturais::Química
Natural sciences::Chemical sciences
URI: https://hdl.handle.net/10216/96349
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FCUP - Artigo em Revista Científica Internacional

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