Interaction mechanism of pepsin with a natural inhibitor gastrodin studied by spectroscopic methods and molecular docking

Wang, Jie; Chan, Calvin; Huang, Fenglan; Xie, Jiangfeng; Xu, Hong; Ho, Ka-wai; Zheng, Sheng-gang; Hu, Zhangli; Lu, Jun; He, Zhendan

doi:10.1007/s00044-016-1760-2

Cited by 20 publications

(8 citation statements)

References 31 publications

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“…1 It was first approved to be listed on the market by U.S. Food and Drug Administration in 2013. 2 As an oral administration drug, dabrafenib has a mean absolute bioavailability of 94.5% at fasting conditions. 3 Dabrafenib is mainly transported by binding with plasma proteins in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Investigation on the Interaction of Dabrafenib with Human Serum Albumin Using Combined Experiment and Molecular Dynamics Simulation: Exploring the Binding Mechanism, Esterase-like Activity, and Antioxidant Activity

et al. 2018

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Dabrafenib is a novel targeted antimelanoma drug. The present work explored the binding mechanism of dabrafenib-human serum albumin (HSA) and the effect on the esterase-like activity and antioxidant activity of HSA by using 19 F NMR, spectroscopy methods, and molecular dynamics simulation. The results of 19 F NMR, fluorescence, and time-resolved fluorescence spectroscopy revealed that dabrafenib spontaneously binds to the subdomain IIIA of the HSA by hydrophobic action and forms a static complex. The binding affects the esterase-like activity of HSA but not its antioxidant activity. According to the results of molecular dynamics simulation, dabrafenib interacts with Arg410 and Tyr411, which are the key residue associated with the esterase-like activity of HSA. Meanwhile, dabrafenib does not interact with Cys34, the key residue associated with the antioxidant activity of HSA. The results of circular dichroism spectroscopy and molecular dynamics simulation show that the conformation of HSA is not affected by the binding of dabrafenib. This study can provide useful information for understanding the pharmacokinetic properties of dabrafenib.

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Section: Introductionmentioning

confidence: 99%

“…Dabrafenib (GSK2118436) is a novel selective inhibitor of BRAF V600E kinase for treating advanced melanoma . It was first approved to be listed on the market by U.S. Food and Drug Administration in 2013 . As an oral administration drug, dabrafenib has a mean absolute bioavailability of 94.5% at fasting conditions .…”

Section: Introductionmentioning

confidence: 99%

Investigation on the Interaction of Dabrafenib with Human Serum Albumin Using Combined Experiment and Molecular Dynamics Simulation: Exploring the Binding Mechanism, Esterase-like Activity, and Antioxidant Activity

et al. 2018

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“…The substrate interacts with the amino acid residues of the protease to occupy the active site and inhibit the activity of the enzyme (Wang et al, 2016b;Mohseni-Shahri et al, 2018). In addition, the binding of food ingredients to enzymes triggers the structure and conformation of the enzyme to change, which can reduce its activity (Wang et al, 2017a). Moreover, the study found that the binding capacity of catechin gallate (EGCG) exceeded that of the other three catechin isomers (epicatechin gallate (ECG), epicatechin (EC) and epigallocatechin (EGC)) that were docked with trypsin.…”

Section: Proteinmentioning

confidence: 99%

Recent developments in molecular docking technology applied in food science: a review

Tao

Huang

Wang

et al. 2019

Int J of Food Sci Tech

150

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Molecular docking is a theoretical simulation method based on bioinformatics, which studies the interaction between molecules (such as ligands and receptors), and predicts their binding modes and affinity via a computer platform. This technology acts as a promising mean in medicinal chemistry such as structurebased rational drug design, which is accepted by researchers in the scientific community. During recent years, various fundamental studies involving biomolecular interaction in the food matrix have gradually emerged. The remarkable advantages of molecular docking such as predicting experiments are attracting increasing attention for its application potential in various fields. This review presents the theory and software development of molecular docking, and emphasises its application in the field of food science, including nutritional components and food safety. Moreover, the operational mechanisms of molecular docking are further summarised in this review.

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“…The interaction between proteins and drug molecules has attracted widespread attention in medicinal chemistry and biology. In the last decade, a variety of analytical methods have been developed for the study of protein complexes, such as NMR, UV–visible and fluorescence spectroscopies among others. NMR can determine the structure of protein complexes, but it has a limitation for the analysis of proteins with relatively low molecular weights and the need of a large sample amount, compared to mass spectrometry (MS).…”

Section: Introductionmentioning

confidence: 99%

Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

Chi

Feng

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Interactions of drug molecules and proteins play important roles in physiological and pathological processes in vivo. It is of significance to establish a reliable strategy for studying protein–drug ligand interactions and would be helpful for the design and screening of new drugs in pharmacological research. Methods The interactions between four indole alkaloids (IAs) extracted from Ophiorrhiza japonica (O. japonica) and myoglobin (Mb) protein were investigated using a multi‐spectrometric and computational method of native electrospray ionization mass spectrometry (native ESI‐MS), hydrogen/deuterium exchange mass spectrometry (HDX‐MS), circular dichroism (CD) and molecular docking (MD). Results The IA‐bound Mb complexes were analyzed using native ESI‐MS, with the obtained protein‐to‐ligand stoichiometry at 1:1, 1:2 and 1:3. Binding constants were measured according to the interpretation of MS spectra. MD complemented MS measurements, probing the binding sites and modes of the four IAs to Mb. Analyses involving CD and HDX‐MS demonstrated that exposure to IAs could affect the conformation of Mb by decreasing the α‐helix content and made Mb more susceptible to HDX at the backbone. Conclusions A new MS‐based integrated analysis method has been developed to successfully study the interactions of Mb and IAs extracted from O. japonica. The experimental and calculation results have good consistency, revealing all of the four IA molecules could bind to Mb to form 1:1, 1:2 and 1:3 Mb–IA complexes. The order of binding ability of these IAs to Mb was ophiorrhine B > compound C > ophiorrhine A > compound D. CD and HDX‐MS results indicated that binding with IAs destabilizes Mb. HDX‐MS analysis suggests that Mb becomes more susceptible to HDX, indicating that binding with IAs destabilizes the structure of Mb. In addition, the interaction with IAs affected the overall structure of Mb, ascribed to the decrease of α‐helix content and less folding of the backbone.

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Interaction mechanism of pepsin with a natural inhibitor gastrodin studied by spectroscopic methods and molecular docking

Cited by 20 publications

References 31 publications

Investigation on the Interaction of Dabrafenib with Human Serum Albumin Using Combined Experiment and Molecular Dynamics Simulation: Exploring the Binding Mechanism, Esterase-like Activity, and Antioxidant Activity

Investigation on the Interaction of Dabrafenib with Human Serum Albumin Using Combined Experiment and Molecular Dynamics Simulation: Exploring the Binding Mechanism, Esterase-like Activity, and Antioxidant Activity

Recent developments in molecular docking technology applied in food science: a review

Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

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