第36卷，第11期 2016年11月
光谱学与光谱分析 Spectroscopy and Spectral Analysis
Vol. 36, No. 11+pp3789-3795
November，2016
Spectroscopic and MolecularDockingStudy on Specific Binding and
InhibitionofIsoniazidtoHumanSerumAlbuminandCatalase
WANG Yi-run',FANG Qing',HU Tao-ying',LIU Yingl-2+
1. College of Life and Environmental Sciences, Minzu University of China, Beijing100081, China
2. Beijing Engineering Research Center of Food Environment and Public Health, Minzu University of China, Beijing 100081, China
Isonicotinic acid hydrazide (Isoniazid, INH) is one of the most commonly used first-line anti-tuber
Abstract
culosis drugs, which has been reported that the high concentration of INH in human body can lead to epilepsy, liver function failure, and even death. Therefore, studying the potential binding effects of INH on the struc ture and activity of human serum albumin (HSA) and catalase (CAT) is very essential for evaluating its toxici-ty and side effect. In this paper, multi-spectroscopic and molecular docking methods were used to elucidate the patterns of INH to HSA and CAT under imitated physiological conditions. The inner filter effect of all fluores cence data in the paper was eliminated to get accurate binding parameters. The Stern-Volmer quenching con stants (Ksv ) of both HSA-INH system and CAT-INH system inversely correlated with temperatures, demon strating that INH quench the intrinsic fluorescence of HSA and CAT via static quenching. The conformational investigation of HSA and CAT through UV-visible absorption spectroscopy, synchronous fluorescence and cir cular dichroism (CD) showed that INH could change the micro-environment of tryptophan residues and re duced the α-helix content of protein. These results demonstrated that the binding of INH may lead to the loos ening of protein skeleton, which which may affect its physiological function. The results of molecular docking revealed that the INH was located in Sudlow's site I of HSA. And INH bound to CAT at a cavity among the wrapping domain helical domain and β-barrel, which resulted in the inhibition of CAT activity. In addition, Levofloxacin (LVFX) is a new effective and safe second-line anti-tuberculosis drugs and can improve the cura tive effect on anti-TB by using with other anti-TB drugs, the result of Hill's coefficients (nn) about synergy between INH and proved that LVFX promoted the interaction of HSA with INH. Moreover, according to the CD spectra, synergy between INH and LVFX changed the conformation of HSA and the amount of α-helix de creased about 7. 9%. This work will provide important insights into the binding and toxicity mechanism of INH to HSA and CAT in vivo and is expected to be helpful in evaluating the essential information for using the
INH safely. Keywords
Isoniazid; Human serum albumin; Catalase; Multi-spectroscopic techniques: Molecular modeling
中图分类号：R113
文献标识码：A
Received: 2016-03-30; aceepted: 2016-0728
D0l: 10. 3964/j.issn.10000593(2016)11-378907
Foundation item: The National Natural Science Foundation of China (21177163) , 111 Project B08044, First-class University First Class Aca
demic Program of Minzu University of China ( YLDX01013), Special Guidance Fund of Building World First-class Universi-ties (Disciplines) and Characteristic Development of Minzu University of China ( 2016), Coordinate Development of First-Class and First-Class University Discipline Construction Funds(10301-0150200604) , The Academie Team Construction Pro-ject of Minzu University of China (2015MDTD25C&.13C), First-class Universities and First-class Discipline Construction Transitional Funds under Special Funding(2016, Ph. D), 2015MDTD08C
Biography : WANG Yi-run, (1989—), Doctor of College of Life and Environmental Sciences, Minzu University of China
万芳数据wang8@125.com
Corresponding author
e-mail : liuying4300@163. com