Interaction of a glutathione S-conjugate with glutathione reductase. Kinetic and X-ray crystallographic studies.
Interaction of a glutathione S-conjugate with glutathione reductase. Kinetic and X-ray crystallographic studies.
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谷胱甘肽 S-缀合物与谷胱甘肽还原酶的相互作用。
DOI：
10.1111/j.1432-1033.1984.tb07925.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Georg E. Schulz
中科院分区：
文献类型：
--
作者：
Manfred Bilzer;R. Krauth;R. Schirmer;T. Akerboom;Helmut Sies;Georg E. Schulz
谷胱甘肽的S-缀合物以至少两种方式影响肝细胞的谷胱甘肽/谷胱甘肽二硫化物（GSH/GSSG）状态，即通过抑制GSSG转运到胆汁中[Akerboom等人（1982）FEBS Lett. 140，73-76]和通过抑制酶GSSG还原酶（EC 1.6.4.2）。GSSG还原酶的相互作用与一个充分研究的共轭物，即S-（2，4-二硝基苯基）-谷胱甘肽及其亲电前体1-氯-2，4-二硝基苯的描述。对于短时间暴露，两种化合物都是酶的可逆抑制剂，Ki值分别为30 μ M和22 μ M。在长时间孵育后，1-氯-2，4-二硝基苯不可逆地阻断GSSG还原酶，这强调了原位快速缀合物形成的需要。如X射线晶体学所示，GSSG还原酶中S-（2，4-二硝基苯基）-谷胱甘肽的主要结合位点与底物谷胱甘肽二硫化物的结合位点重叠。然而，缀合物的谷胱甘肽部分不以与二硫化物中的任一谷胱甘肽相同的方式结合。
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). 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 Ki values being 30 microM and 22 microM respectively. After prolonged incubation, 1-chloro-2,4-dinitrobenzene blocks GSSG reductase irreversibly, which emphasizes the need for rapid conjugate formation in situ. 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.
影响因子：
2.9
作者：
REED, DJ;BABSON, JR;POTTER, DW
通讯作者：
POTTER, DW
影响因子：
2.9
作者：
GEKKO, K;TIMASHEFF, SN
通讯作者：
TIMASHEFF, SN