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Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate.
- Source :
-
Structure (London, England : 1993) [Structure] 1995 Jul 15; Vol. 3 (7), pp. 717-27. - Publication Year :
- 1995
-
Abstract
- Background: Glutathione transferases (GSTs) constitute a family of isoenzymes that catalyze the conjugation of the tripeptide glutathione with a wide variety of hydrophobic compounds bearing an electrophilic functional group. Recently, a number of X-ray structures have been reported which have defined both the glutathione- and the substrate-binding sites in these enzymes. The structure of the glutathione-free enzyme from a mammalian source has not, however, been reported previously.<br />Results: We have solved structures of a human alpha-class GST, isoenzyme A1-1, both in the unliganded form and in complexes with the inhibitor ethacrynic acid and its glutathione conjugate. These structures have been refined to resolutions of 2.5 A, 2.7 A and 2.0 A respectively. Both forms of the inhibitor are clearly present in the associated electron density.<br />Conclusions: The major differences among the three structures reported here involve the C-terminal alpha-helix, which is a characteristic of the alpha-class enzyme. This helix forms a lid over the active site when the hydrophobic substrate binding site (H-site) is occupied but it is otherwise disordered. Ethacrynic acid appears to bind in a non-productive mode in the absence of the coenzyme glutathione.
- Subjects :
- Apoenzymes metabolism
Binding Sites
Crystallography, X-Ray methods
Ethacrynic Acid analogs & derivatives
Humans
Isoenzymes metabolism
Macromolecular Substances
Models, Molecular
Apoenzymes chemistry
Ethacrynic Acid metabolism
Glutathione analogs & derivatives
Glutathione metabolism
Glutathione Transferase chemistry
Glutathione Transferase metabolism
Isoenzymes chemistry
Protein Structure, Secondary
Subjects
Details
- Language :
- English
- ISSN :
- 0969-2126
- Volume :
- 3
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 8591048
- Full Text :
- https://doi.org/10.1016/s0969-2126(01)00206-4