GSTP1‐1 stereospecifically catalyzes glutathione conjugation of ethacrynic acid

FEBS Letters

van Iersel, Marlou L.P.S²  Vervoort, Jacques¹  van Lipzig, Marola M.H²  Rietjens, Ivonne M.C.M¹  van Bladeren, Peter J² 

[1] Laboratory of Biochemistry, Department of Biomolecular Sciences, Wageningen Agricultural University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands;Toxicology Group, Department of Food Technology and Nutritional Sciences, Wageningen Agricultural University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands

关键词: Stereoselectivity;    Glutathione S-transferase;    Ethacrynic acid;    EA;    ethacrynic acid;    EASG;    ethacrynic acid-glutathione conjugate;    GSH;    glutathione;    GST;    glutathione S-transferase;    GSTA and GSTα;    alpha-class glutathione S-transferases;    GSTP and GSTπ;    pi-class glutathione S-transferases;    Int.;    intermediate;   

DOI  :  10.1016/S0014-5793(98)01546-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using ¹H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one of the diastereoisomers (A). The GSTP1-1 mutant C47S and GSTA1-1 preferentially form the same diastereoisomer of EASG as GSTP1-1. Glutathione conjugation of EA by GSTA1-2 and GSTA2-2 is not stereoselective. When human melanoma cells, expressing GSTP1-1, were exposed to ethacrynic acid, diastereoisomer A was the principal conjugate formed, indicating that even at physiological pH the enzyme catalyzed reaction dominates over the chemical conjugation.

【 授权许可】

Unknown