化学
谷胱甘肽
重氮
酶
合作性
酶动力学
谷胱甘肽还原酶
立体化学
生物化学
动力学
组合化学
生物物理学
活动站点
药物化学
谷胱甘肽过氧化物酶
生物
物理
量子力学
作者
Mohammed H. Alqarni,Ahmed I. Foudah,Magdy Mohamed Muharram,Nikolaos E. Labrou
出处
期刊:Molecules
[MDPI AG]
日期:2021-04-20
卷期号:26 (8): 2399-2399
被引量:4
标识
DOI:10.3390/molecules26082399
摘要
Human glutathione transferase A1-1 (hGSTA1-1) contributes to developing resistance to anticancer drugs and, therefore, is promising in terms of drug-design targets for coping with this phenomenon. In the present study, the interaction of anthraquinone and diazo dichlorotriazine dyes (DCTD) with hGSTA1-1 was investigated. The anthraquinone dye Procion blue MX-R (PBMX-R) appeared to interact with higher affinity and was selected for further study. The enzyme was specifically and irreversibly inactivated by PBMX-R, following a biphasic pseudo-first-order saturation kinetics, with approximately 1 mol of inhibitor per mol of the dimeric enzyme being incorporated. Molecular modeling and protein chemistry data suggested that the modified residue is the Cys112, which is located at the entrance of the solvent channel at the subunits interface. The results suggest that negative cooperativity exists upon PBMX-R binding, indicating a structural communication between the two subunits. Kinetic inhibition analysis showed that the dye is a competitive inhibitor towards glutathione (GSH) and mixed-type inhibitor towards 1-chloro-2,4-dinitrobenzene (CDNB). The present study results suggest that PBMX-R is a useful probe suitable for assessing by kinetic means the drugability of the enzyme in future drug-design efforts.
科研通智能强力驱动
Strongly Powered by AbleSci AI