Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/35623
Title: Exploring the molecular mechanism of hA1-1 glutathione S-transferase, focusing on the role of the characteristic C-terminal helix.
Authors: Allardyce, Claire S.
Award date: 1996
Presented at: University of Leicester
Abstract: The molecular mechanism of hAl-1 glutathione S-transferase (GST) has been probed using fluorescence and NMR spectroscopy, kinetic analysis and X-ray crystallography. The results show that the mechanism of hAl-1 GST involves hydrophobic substrate activation, and the efficiency of this process is a crucial factor in hydrophobic substrate specificity. Hydrophobic substrate activation can only occur when the glutathione peptidyl moiety has bound, inducing a conformational change in the protein. The main region of the protein that is involved in this conformational change is the characteristic C-terminal helix of hAl-1 GST and the integrity of this region has been shown to be essential for hydrophobic substrate activation. It is thought that the C-terminal helix correctly orientates the hydrophobic substrate in the active site allowing activation to occur. The deletion of the C-terminal helix alters the substrate specificity of the enzyme, with the truncated enzyme having a high activity towards ethacrynic acid, normally a pi-class GST substrate. Thus the characteristic C-terminal helix of alpha class GSTs is a major determinant in substrate specificity, in particular determining the characteristic substrate specificity of hAl-1 GST.
Links: http://hdl.handle.net/2381/35623
Type: Thesis
Level: Doctoral
Qualification: Ph.D.
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, School of Education
Leicester Theses

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