Journal article

Contribution of glycine 146 to a conserved folding module affecting stability and refolding of human glutathione transferase P1-1

GKW Kong, G Polekhina, WJ McKinstry, MT Parker, B Dragani, A Aceto, D Paludi, DR Principe, B Mannervik, G Stenberg

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2003

Abstract

In human glutathione transferase P1-1 (hGSTP1-1) position 146 is occupied by a glycine residue, which is located in a bend of a long loop that together with the alpha6-helix forms a substructure (GST motif II) maintained in all soluble GSTs. In the present study G146A and G146V mutants were generated by site-directed mutagenesis in order to investigate the function played by this conserved residue in folding and stability of hGSTP1-1. Crystallographic analysis of the G146V variant, expressed at the permissive temperature of 25 degrees C, indicates that the mutation causes a substantial change of the backbone conformation because of steric hindrance. Stability measurements indicate that this ..

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