Title
GSTP1-1 stereospecifically catalyzes glutathione conjugation of ethacrynic acid
Author
van Iersel, M.L.P.S.
van Lipzig, M.M.H.
Rietjens, I.M.C.M.
Vervoort, J.
van Bladeren, P.J.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
1998
Abstract
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. Copyright (C) 1998 Federation of European Biochemical Societies.
Subject
EA, ethacrynic acid
Ethacrynic acid
Glutathione S-transferase
Stereoselectivity
Etacrynic acid
Glutathione
Glutathione transferase
Multidrug resistance protein
Chemical reaction
Conjugate
Controlled study
Diastereoisomer
Drug conjugation
Enzyme mechanism
Glutathione metabolism
Human cell
Melanoma cell
Nuclear magnetic resonance spectroscopy
Stereochemistry
Amino Acid Substitution
Ethacrynic Acid
Glutathione
Glutathione Transferase
Humans
Isoenzymes
Melanoma
Point Mutation
Stereoisomerism
Substrate Specificity
Tumor Cells, Cultured
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http://resolver.tudelft.nl/uuid:2b31fb1a-7e5a-41f0-afbb-e65823d74395
DOI
https://doi.org/10.1016/s0014-5793(98)01546-4
TNO identifier
234853
ISSN
0014-5793
Source
FEBS Letters, 441 (1), 153-157
Document type
article