Glutathione transferase A1-1: catalytic role of water

• Type: Article in International Scientific Journal
• Date: 2009

Authors

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

Journal

Title: Theoretical Chemistry Accounts

Vol. 124

Pages: 71-83

ISSN: 1432-881X

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 7 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-003-GJV

DOI: 10.1007/s00214-009-0582-4

Abstract (EN): For more than almost 30 years now, glutathione transferases (GSTs) have been known as xenobiotic/endobiotic detoxification enzymes. GSTs catalyze the nucleophilic addition of glutathione (GSH) sulphur thiolate to a wide range of electrophilic substrates, building up a less toxic and more soluble compound, which can then be removed from the cell. Recently we proposed a consistent GSH activation mechanism. By performing QM/MM calculations, we demonstrated that a water molecule, following a first conformational rearrangement of GSH, is capable of assisting a proton transfer between the GSH thiol and alpha carboxylic groups. In this study we go further in the analysis of the water role in GSH activation by performing a long Molecular Dynamics (MD) study on glutathione transferase A1-1 Thr68 mutants complexed with GSH and the GSH decarboxylated analogue (dGSH), for which experimental kinetic data are available.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13