Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/96349
Autor(es): | Daniel F A R Dourado Pedro Alexandrino Fernandes Bengt Mannervik Maria Joao Ramos |
Título: | Glutathione Transferase A1-1: Catalytic Importance of Arginine 15 |
Data de publicação: | 2010 |
Resumo: | 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. |
Assunto: | Química Chemical sciences |
Áreas do conhecimento: | Ciências exactas e naturais::Química Natural sciences::Chemical sciences |
URI: | https://hdl.handle.net/10216/96349 |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | restrictedAccess |
Aparece nas coleções: | FCUP - Artigo em Revista Científica Internacional |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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49521.pdf Restricted Access | 3.23 MB | Adobe PDF | Request a copy from the Author(s) |
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