Article
Multidisciplinary Sciences
Jing Li, Rong Shen, Bharat Reddy, Eduardo Perozo, Benoit Roux
Summary: This study investigates the structural and functional impacts of disease-associated mutations on C-type inactivation in the hERG channel using a combination of molecular dynamics simulations, free energy landscape calculations, and electrophysiological experiments. The results suggest that C-type inactivation is associated with a specific conformation of the selectivity filter, and that the degree of opening of the intracellular gate plays a key role in this process. Comparisons with other K+ channels indicate the importance of filter-gate allosteric coupling in C-type inactivation.
Article
Chemistry, Analytical
Tingting Pan, Min Shen, Jiayan Shi, Juewei Ning, Fengyu Su, Jianxiang Liao, Yanqing Tian
Summary: Researchers developed K+ fluorescent nanoprobes for intracellular K+ sensing and imaging, and constructed an easy-operating and biocompatible method for measuring human ether-a-go-go-related gene (hERG) channel activity. This method was efficient for screening hERG channel inhibitors and imaging K+ channel activity in cancer cells.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Biotechnology & Applied Microbiology
Cedric Dzidzor Kodjo Amengor, Emmanuel Orman, Cynthia Amaning Danquah, Inemesit Okon Ben, Prince Danan Biniyam, Benjamin Kingsley Harley
Summary: In this study, pyridine-N-oxide alkaloids from Allium stipitatum and their synthetic disulfide analogs were investigated as potential next-generational antimycobacterial agents. In silico studies, molecular docking simulations, and molecular descriptor analysis were conducted to determine their binding affinities and properties. The results suggested that these compounds have strong binding affinities and favorable properties, making them promising lead candidates for the treatment of multidrug-resistant tuberculosis.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Jan Maly, Aiyana M. Emigh, Kevin R. DeMarco, Kazuharu Furutani, Jon T. Sack, Colleen E. Clancy, Igor Vorobyov, Vladimir Yarov-Yarovoy
Summary: The voltage-gated potassium channel hERG plays a crucial role in membrane repolarization of cardiac myocytes. By using Rosetta modeling, researchers investigated the conformational changes and drug binding mechanisms associated with hERG channel inactivation. The study provides insights into the structural changes and ligand interactions of hERG in the inactivated state.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Aiyana M. Emigh Cortez, Kevin R. Demarco, Kazuharu Furutani, Slava Bekker, Jon T. Sack, Heike Wulff, Colleen E. Clancy, Igor Vorobyov, Vladimir Yarov-Yarovoy
Summary: The human ether-a-go-go-related gene (hERG) is crucial for normal electrical activity in the heart but can also be targeted by drugs. This study utilized computational methods to build structural models of hERG channel in different conformational states and investigated the interactions between drugs and the channel. The findings provide important insights into differentiating safe and harmful hERG blockers based on their structural interactions.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bernd J. Zuenkler, Maria Wos-Maganga, Stefanie Bohnet, Anne Kleinau, Detlef Manns, Shivani Chatterjee
Summary: This study investigates the binding sites of blockers for hERG and K-ATP channels from the cytoplasmic side of the plasma membrane. It reveals the presence of intracellular binding sites for these channels that cannot be dialyzed by the patch-pipette solution.
JOURNAL OF MEMBRANE BIOLOGY
(2023)
Article
Chemistry, Applied
Jinpeng Zhu, Zhentian Li, Caie Wu, Gongjian Fan, Tingting Li, Dongbei Shen, Jinfeng Dou, Yi Liang
Summary: In this study, the binding mechanism in zein/rutin complexes was systematically studied using multi-spectroscopic methods and molecular simulations. Results showed that the encapsulation efficiency of complexes reached a maximum of 67.30% when the concentration of rutin was 60 μM. Microstructure characterization revealed a spherical morphology of the complexes. Multi-spectroscopic experiments indicated the occurrence of static quenching and strong affinity in the interaction process. Molecular dynamics simulation further confirmed hydrophobic interaction as the main force in zein/rutin complexes. This work is important for the utilization of zein for the delivery of bio-compounds.
Article
Multidisciplinary Sciences
Victoria Amstrup Vold, Sebastian Glanville, Dan Arne Klaerke, Per Amstrup Pedersen
Summary: In order to solve the problem of obtaining sufficient ultra-pure protein for structural studies of membrane proteins, a dual-function plasmid, pXOOY, was constructed for protein production in yeast and electrophysiology in oocytes. The plasmid combines elements from a Xenopus-mammalian vector and a high-yield yeast expression vector. The performance of pXOOY was evaluated and it was found that it led to higher accumulation of the expressed channels in yeast cells and maintained channel activity in oocytes.
Article
Biology
Julian Alexander Schreiber, Anastasia Derksen, Gunnar Goerges, Sven Schuette, Jasmin Soergel, Aytug K. Kiper, Nathalie Strutz-Seebohm, Tobias Ruck, Sven G. Meuth, Niels Decher, Guiscard Seebohm
Summary: It is reported that the drug cloxyquin activates the TWIK-related spinal cord K+ channel (TRESK) by stabilizing the inner selectivity filter. This finding has significant implications for future drug development.
COMMUNICATIONS BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Simona Saponara, Fabio Fusi, Daniele Iovinelli, Amer Ahmed, Alfonso Trezza, Ottavia Spiga, Giampietro Sgaragli, Massimo Valoti
Summary: The cardiac action potential is regulated by various ion channels. Drugs that block these channels, especially the hERG channel, may cause potentially lethal ventricular arrhythmias. Flavonoids, commonly found in food and beverages, have been shown to interact with and block the hERG-channel current, despite escaping traditional assessments.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Environmental Sciences
Wenjing Chen, Xiaosong Zhao, Weihui Xu, Yunlong Hu, Ruixing Hou, Zhigang Wang
Summary: In this study, the impact of DMP on the uptake and metabolism of sugars in E. coli K-12 was assessed. The results showed that DMP contamination inhibited the growth of E. coli K-12 and decreased the uptake and utilization of sugars. Carbon metabolism and oxidative phosphorylation were also affected by DMP.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Wendy W. Wu, Moran Choe, Lars Johannesen, Jose Vicente, Girish Bende, Norman L. Stockbridge, David G. Strauss, Christine Garnett
Summary: The study found that hERG and ventricular repolarization assays cannot predict clinical QT(C) prolongation potential for peptides and proteins. Peptides and proteins, regardless of size, have a low likelihood of direct cardiac ion channel interactions, similar to large targeted proteins and monoclonal antibodies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Shruti Koulgi, Vinod Jani, Vinay Nair, Jagmohan S. Saini, Samiron Phukan, Uddhavesh Sonavane, Rajendra Joshi, Raj Kamboj, Venkata Palle
Summary: Evaluation of cardiotoxicity potential of new chemical entities has become a stringent filter in drug discovery, with a focus on hERG channel protein inhibition. A computational model for the active-state of hERG was developed and showed noticeable conformational changes in the protein upon ligand-binding, potentially leading to a collapse of the pore and transition of hERG from an open to an inactive state. These findings could aid in designing compounds devoid of hERG inhibition and reduced cardiotoxicity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Food Science & Technology
Wenli Shi, Guowen Zhang, Yijing Liao, Xiaoyun Fei, Deming Gong, Xing Hu
Summary: Kaempferol, a natural flavonoid compound, was found to reversibly inhibit the activity of AChE through the formation of a complex with the enzyme, leading to a decrease in its catalytic activity. Additionally, kaempferol was found to increase the binding affinity of other drugs to AChE, resulting in a synergistic inhibition of its activity. This study provides new insights into the potential use of kaempferol as a functional food component for the treatment of AD.
Article
Genetics & Heredity
Janina Sormann, Marcus Schewe, Peter Proks, Thibault Jouen-Tachoire, Shanlin Rao, Elena B. Riel, Katherine E. Agre, Amber Begtrup, John Dean, Maria Descartes, Jan Fischer, Alice Gardham, Carrie Lahner, Paul R. Mark, Srikanth Muppidi, Pavel N. Pichurin, Joseph Porrmann, Jens Schallner, Kirstin Smith, Volker Straub, Pradeep Vasudevan, Rebecca Willaert, Elisabeth P. Carpenter, Karin E. J. Rodstrom, Michael G. Hahn, Thomas Mueller, Thomas Baukrowitz, Matthew E. Hurles, Caroline F. Wright, Stephen J. Tucker
Summary: Sleep apnea, a common disorder with significant public health burden, has been associated with rare gain-of-function mutations in the KCNK3 gene, highlighting a new role for TASK-1 K+ channels and presenting possible therapeutic strategies.
