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The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase P1‐1 in two different modes
Author(s) -
Oakley Aaron J,
Lo Bello Mario,
Mazzetti Anna Paola,
Federici Giorgio,
Parker Michael W
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01424-5
Subject(s) - conjugate , glutathione , moiety , chemistry , enzyme , glutathione s transferase , transferase , stereochemistry , biochemistry , mathematics , mathematical analysis
The diuretic drug ethacrynic acid, an inhibitor of pi class glutathione S ‐transferase, has been tested in clinical trials as an adjuvant in chemotherapy. We recently solved the crystal structure of this enzyme in complex with ethacrynic acid and its glutathione conjugate. Here we present a new structure of the ethacrynic‐glutathione conjugate complex. In this structure the ethacrynic moiety of the complex is shown to bind in a completely different orientation to that previously observed. Thus there are at least two binding modes possible, an observation of great importance to the design of second generation inhibitors of the enzyme.