The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase P1‐1 in two different modes

FEBS Letters

Oakley, Aaron J³  Parker, Michael W³  Federici, Giorgio²  Lo Bello, Mario¹  Mazzetti, Anna Paola¹ 

[1] Department of Biology, University of Rome ‘Tor Vergata’, Via della Ricerca Scientifica, 00133 Rome, Italy;Ospedale Pediatrico IRCCS ‘Bambin Gesù’, 00165 Rome, Italy;The Ian Potter Foundation Protein Crystallography Laboratory, St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia

关键词: Drug design;    Ethacrynic acid;    Enzyme-inhibitor complex;    Glutathione transferase;    X-ray structure;    Human;   

DOI  :  10.1016/S0014-5793(97)01424-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown