Glutathione Transferase A1-1: Catalytic Importance of Arginine 15

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Daniel F A R Dourado (Author) Other; Pedro Alexandrino Fernandes (Author) FCUP; Bengt Mannervik (Author) Other; Maria Joao Ramos (Author) FCUP

Journal

Title: Journal of Physical Chemistry B

Vol. 114 No. 1

Pages: 1690-1697

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 17 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-003-961

DOI: 10.1021/jp908251z

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8