Cryo-EM Structure of K+-Bound hERG Channel Complexed with the Blocker Astemizole.
Tatsuki Asai,Naruhiko Adachi,Toshio Moriya,Hideyuki Oki,Takamitsu Maru,Masato Kawasaki,Kano Suzuki,Sisi Chen,Ryohei Ishii,Kazuko Yonemori,Shigeru Igaki,Satoshi Yasuda,Satoshi Ogasawara,Toshiya Senda,Takeshi Murata +14 more
Reads0
Chats0
TLDR
In this paper, the authors obtained the 3.5-A density map of a potassium-bound hERG channel complexed with astemizole, a well-known hERG inhibitor that increases risk of potentially fatal arrhythmia.About:
This article is published in Structure.The article was published on 2021-03-04 and is currently open access. It has received 29 citations till now. The article focuses on the topics: hERG & Astemizole.read more
Citations
More filters
Journal ArticleDOI
Structural Insights into the Mechanisms and Pharmacology of K2P Potassium Channels.
TL;DR: The K2P (KCNK) channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs.
Journal ArticleDOI
Structure-Based Prediction of hERG-Related Cardiotoxicity: A Benchmark Study.
Teresa Maria Creanza,Pietro Delre,Nicola Ancona,Giovanni Lentini,Michele Saviano,Giuseppe Felice Mangiatordi +5 more
TL;DR: In this article, the authors presented the first structure-based classifiers able to distinguish hERG binders from non-binders by integrating docking scores and protein-ligand interaction fingerprints through a SVM LASSO regularized strategy.
Journal ArticleDOI
Membranes under the Magnetic Lens: A Dive into the Diverse World of Membrane Protein Structures Using Cryo-EM
TL;DR: Insight is provided into how the recent advances in membrane biology and biochemistry, as well as technical advances in cryo-electron microscopy, help to solve structures of a large variety of membrane protein groups, from small receptors to large transporters and more complex machineries.
Journal ArticleDOI
Molecular determinants of pro-arrhythmia proclivity of d- and l-sotalol via a multi-scale modeling pipeline.
Kevin R. DeMarco,Pei Chi Yang,Vikrant Singh,Kazuharu Furutani,Kazuharu Furutani,John R. D. Dawson,Mao Tsuen Jeng,James C. Fettinger,Slava Bekker,Slava Bekker,Van A. Ngo,Sergei Y. Noskov,Vladimir Yarov-Yarovoy,Jon T. Sack,Heike Wulff,Colleen E. Clancy,Igor Vorobyov +16 more
TL;DR: In this article, the authors developed a multi-scale in silico pipeline focusing on hERG channel -drug interactions and used it to probe and predict the mechanisms of proarrhythmia risks of the two enantiomers of sotalol.
Journal ArticleDOI
hERG Blockade Prediction by Combining Site Identification by Ligand Competitive Saturation and Physicochemical Properties.
TL;DR: Uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade leads to improved model predictability based on Pearson’s R and percent correct metric for different validation sets of hERG blockers involving a diverse chemical scaffold and wide range of pIC50 values.
References
More filters
Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI
MotionCor2: Anisotropic Correction of Beam-Induced Motion for Improved Cryo-Electron Microscopy
Shawn Q. Zheng,Eugene Palovcak,Jean Paul Armache,Kliment A. Verba,Yifan Cheng,David A. Agard +5 more
TL;DR: MotionCor2 software corrects for beam-induced sample motion, improving the resolution of cryo-EM reconstructions.
Journal ArticleDOI
Structure validation by Calpha geometry: phi,psi and Cbeta deviation.
Simon C. Lovell,Ian W. Davis,W. Bryan Arendall,Paul I.W. de Bakker,J. Michael Word,Michael G. Prisant,Jane S. Richardson,David S. Richardson +7 more
TL;DR: Geometrical validation around the Cα is described, with a new Cβ measure and updated Ramachandran plot, and Favored and allowed ϕ,ψ regions are also defined for Pro, pre‐Pro, and Gly (important because Gly ϕ‐ψ angles are more permissive but less accurately determined).
Related Papers (5)
Cryo-EM Structure of the Open Human Ether-a-go-go-Related K(+) Channel hERG.
Weiwei Wang,Roderick MacKinnon +1 more