Dataset Information

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.

SUBMITTER: Guo L

PROVIDER: S-EPMC7087788 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods.

Guo Liuqi L Ma Xiaoli X Yan Jin J Xu Kailin K Wang Qing Q Li Hui H

Journal of fluorescence 20150926 6

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. Mol ...[more]

PMID: 26410777

Similar Datasets

Project description:Aspergillus fumigatus biofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treat Aspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study, in vitro interactions between polyene antifungals (AMB and LAMB) and alginate lyase (AlgL), an enzyme degrading the polysaccharides produced as extracellular polymeric substances (EPSs) within the biofilm matrix, against A. fumigatus biofilms were evaluated by using the checkerboard microdilution and the time-kill assays. Furthermore, atomic force microscopy (AFM) was used to image and quantify the effects of AlgL-antifungal combinations on biofilm-growing hyphal cells. On the basis of fractional inhibitory concentration index values, synergy was found between both AMB formulations and AlgL, and this finding was also confirmed by the time-kill test. Finally, AFM analysis showed that when A. fumigatus biofilms were treated with AlgL or polyene alone, as well as with their combination, both a reduction of hyphal thicknesses and an increase of adhesive forces were observed compared to the findings for untreated controls, probably owing to the different action by the enzyme or the antifungal compounds. Interestingly, marked physical changes were noticed in A. fumigatus biofilms exposed to the AlgL-antifungal combinations compared with the physical characteristics detected after exposure to the antifungals alone, indicating that AlgL may enhance the antibiofilm activity of both AMB and LAMB, perhaps by disrupting the hypha-embedding EPSs and thus facilitating the drugs to reach biofilm cells. Taken together, our results suggest that a combination of AlgL and a polyene antifungal may prove to be a new therapeutic strategy for invasive aspergillosis, while reinforcing the EPS as a valuable antibiofilm drug target.

Dataset Information

Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods.

Publications

Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets