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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/16296
Title: An electron-sharing network involved in the catalytic mechanism is functionally conserved in different glutathione transferase classes
Authors: Pakorn Winayanuwattikun
Albert J. Ketterman
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 9-Sep-2005
Citation: Journal of Biological Chemistry. Vol.280, No.36 (2005), 31776-31782
Abstract: In Anopheles dirus glutathione transferase D3-3, there are electrostatic interactions between the negatively charged glutamyl α-carboxylate group of glutathione, the positively charged Arg-66, and the negatively charged Asp-100. This ionic interaction is stabilized by a network of hydrogen bonds from Ser-65, Thr-158, Thr-162, and a conserved water-mediated contact. This alternating ionic bridge interaction between negatively and positively charged residues stabilized by a network of hydrogen bonding we have named an electron-sharing network. We show that the electron-sharing network assists the glutamyl α-carboxylate of glutathione to function as a catalytic base accepting the proton from the thiol group forming an anionic glutathione, which is a crucial step in the glutathione transferase (GST) catalysis. Kinetic studies demonstrate that the mutation of electron-sharing network residues results in a decreased ability to lower the pKa of the thiol group of glutathione. Although the residues that contribute to the electron-sharing network are not conserved in the primary sequence, structural characterizations indicate that the presence of the network can be mapped to the same region in all GST classes. A structural diversification but functional conservation suggests & significant role for the electron-sharing network in catalysis as the purpose was maintained during the divergent evolution of GSTs. This network appears to be a functionally conserved motif that contributes to the "base-assisted deprotonationα model suggested to be essential for the glutathione ionization step of the catalytic mechanism. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=24744441319&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/16296
ISSN: 00219258
Appears in Collections:Scopus 2001-2005

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