Open AccessInteraction of a glutathione S ‐conjugate with glutathione reductase Kinetic and X‐ray crystallographic studies
Author(s) -
BILZER Manfred,
KRAUTHSIEGEL R. Luise,
SCHIRMER R. Heiner,
AKERBOOM Theo P. M.,
SIES Helmut,
SCHULZ Georg E.
Publication year - 1984
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1984.tb07925.x
Subject(s) - glutathione , glutathione reductase , glutathione disulfide , chemistry , glutaredoxin , conjugate , dinitrophenyl , reductase , enzyme , stereochemistry , moiety , dinitrobenzene , biochemistry , organic chemistry , glutathione peroxidase , biology , mathematical analysis , mathematics , antibody , immunology
1 S‐Conjugates of glutathione influence the glutathione/glutathione disulfide (GSH/GSSG) status of hepatocytes in at least two ways, namely by inhibition of GSSG transport into the bile [Akerboom et al. (1982) FEBS Lett. 140 , 73–76] and by inhibition of the enzyme GSSG reductase (EC 1.6.4.2). 2 The interaction of GSSG reductase with a well‐studied conjugate, namely S ‐(2,4‐dinitrophenyl)‐glutathione and its electrophilic precursor 1‐chloro‐2,4‐dinitrobenzene are described. For short exposures both compounds are reversible inhibitors of the enzyme, the K i values being 30 μM and 22 μM respectively. After prolonged incubation, 1‐chloro‐2,4‐dinitrobenzene blocks GSSG reductase irreversibly, which emphasizes the need for rapid conjugate formation in situ.3 As shown by X‐ray crystallography the major binding site of S ‐(2,4‐dinitrophenyl)‐glutathione in GSSG reductase overlaps the binding site of the substrate, glutathione disulfide. However, the glutathione moiety of the conjugate does not bind in the same manner as either of the glutathiones in the disulfide.