Douglas K T, Al-Timari A, D'Silva C, Gohel D I
Biochem J. 1982 Nov 1;207(2):323-29. doi: 10.1042/bj2070323.
A number of S-substituted glutathiones and the corresponding N-substituted S-substituted analogues have been found to be linear competitive inhibitors of yeast glyoxalase I at 26 degrees C over the pH range 4.6-8.5. N-Acetylation of S-(p-bromobenzyl)glutathione weakens binding by 13.7-fold. N-benzoylation by 25.6-fold, N-trimethylacetylation by 53.3-fold and N-carbobenzoxylation by 7.8-fold, indicating a minor steric component in the binding at the N-site. The Ki-weakening effect of N-substitution of glutathione depends on the chemical nature of the S-substituent, indicating flexibility in the glutathione and/or glyoxalase I contributions to the binding site for glutathione derivatives. The effect of N-acylation on Ki is in accord with a charge interaction of the free enzyme with S-blocked glutathione in a region of reasonably high dielectric constant. There is a slight pH effect on Ki for S-(m-trifluoromethylbenzyl)glutathione but not for S-(p-bromobenzyl)glutathione.
已发现多种S-取代谷胱甘肽及其相应的N-取代S-取代类似物在26℃、pH值4.6 - 8.5范围内是酵母乙二醛酶I的线性竞争性抑制剂。S-(对溴苄基)谷胱甘肽的N-乙酰化使结合减弱13.7倍。N-苯甲酰化减弱25.6倍,N-三甲基乙酰化减弱53.3倍,N-苄氧羰基化减弱7.8倍,这表明在N位点的结合中存在较小的空间位阻成分。谷胱甘肽N-取代对Ki的减弱作用取决于S-取代基的化学性质,这表明谷胱甘肽和/或乙二醛酶I对谷胱甘肽衍生物结合位点的贡献具有灵活性。N-酰化对Ki的影响符合游离酶与S-封闭谷胱甘肽在介电常数较高区域的电荷相互作用。对于S-(间三氟甲基苄基)谷胱甘肽,Ki有轻微的pH效应,而对于S-(对溴苄基)谷胱甘肽则没有。