title: Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods.
abstract: The interaction between niclosamide (NIC) and pepsin was investigated using multispectroscopic and molecular docking methods. Binding constant, number of binding sites, and thermodynamic parameters at different temperatures were measured. Results of fluorescence quenching and synchronous fluorescence spectroscopy in combination with three-dimensional fluorescence spectroscopy showed that changes occurred in the microenvironment of tryptophan residues and the molecular conformation of pepsin. Molecular interaction distance and energy-transfer efficiency between pepsin and NIC were determined based on Förster nonradiative energy-transfer mechanism. Furthermore, the binding of NIC inhibited pepsin activity in vitro. All these results indicated that NIC bound to pepsin mainly through hydrophobic interactions and hydrogen bonds at a single binding site. In conclusion, this study provided substantial molecular-level evidence that NIC could induce changes in pepsin structure and conformation.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China.
authors.forename: Liuqi
authors.initials: L
authors.lastname: Guo
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, People's Republic of China. lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D062105:Molecular Docking Simulation; D009534:Niclosamide / Q000378:metabolism* / Q000494:pharmacology; D010434:Pepsin A / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D012492:Salts / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013552:Swine
chemical_list: D012492:Salts; D009534:Niclosamide; D010434:Pepsin A
keywords: Binding; Fluorescence spectroscopy; Molecular modeling; Niclosamide; Pepsin