{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:47:49Z","timestamp":1791002869746,"version":"4.1.0"},"reference-count":98,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":371,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"Westlake University"},{"name":"Westlake Education Foundation"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Cell"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.molcel.2020.10.037","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T10:36:08Z","timestamp":1606214168000},"page":"25-37.e4","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":99,"title":["Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs"],"prefix":"10.1016","volume":"81","author":[{"given":"Tian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlei","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1216-5393","authenticated-orcid":false,"given":"Huaizong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molcel.2020.10.037_bib1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.molcel.2020.10.037_bib2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1054-3589(08)60281-1","article-title":"Pharmacology of the neurotransmitter release enhancer linopirdine (DuP 996), and insights into its mechanism of action","volume":"35","author":"Aiken","year":"1996","journal-title":"Adv. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib3","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1126\/science.1249410","article-title":"Structure of the yeast mitochondrial large ribosomal subunit","volume":"343","author":"Amunts","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.10.037_bib4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0896-6273(00)80981-2","article-title":"Voltage-gated ion channels and electrical excitability","volume":"20","author":"Armstrong","year":"1998","journal-title":"Neuron"},{"key":"10.1016\/j.molcel.2020.10.037_bib5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev-pharmtox-010617-052912","article-title":"KCNQ-encoded potassium channels as therapeutic targets","volume":"58","author":"Barrese","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.molcel.2020.10.037_bib6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.279.5349.403","article-title":"A potassium channel mutation in neonatal human epilepsy","volume":"279","author":"Biervert","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.10.037_bib7","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/cmdc.201900112","article-title":"Sulfide analogues of flupirtine and retigabine with nanomolar KV 7.2\/KV 7.3 channel opening activity","volume":"14","author":"Bock","year":"2019","journal-title":"ChemMedChem"},{"key":"10.1016\/j.molcel.2020.10.037_bib8","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/j.1528-1167.2012.03441.x","article-title":"The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels","volume":"53","author":"Brickel","year":"2012","journal-title":"Epilepsia"},{"key":"10.1016\/j.molcel.2020.10.037_bib9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/283673a0","article-title":"Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone","volume":"283","author":"Brown","year":"1980","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.10.037_bib10","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/j.1476-5381.2009.00111.x","article-title":"Neural KCNQ (Kv7) channels","volume":"156","author":"Brown","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ng0198-53","article-title":"A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family","volume":"18","author":"Charlier","year":"1998","journal-title":"Nat. Genet."},{"key":"10.1016\/j.molcel.2020.10.037_bib12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","article-title":"High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy","volume":"135","author":"Chen","year":"2013","journal-title":"Ultramicroscopy"},{"key":"10.1016\/j.molcel.2020.10.037_bib13","doi-asserted-by":"crossref","first-page":"19411","DOI":"10.1074\/jbc.RA118.005401","article-title":"Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates KCNQ3 K+ channels by interacting with four cytoplasmic channel domains","volume":"293","author":"Choveau","year":"2018","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib14","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/hmg\/8.7.1321","article-title":"Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families","volume":"8","author":"Coucke","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.molcel.2020.10.037_bib15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s40801-016-0068-3","article-title":"Survey of physicians\u2019 understanding of specific risks associated with retigabine","volume":"3","author":"Daniluk","year":"2016","journal-title":"Drugs Real World Outcomes"},{"key":"10.1016\/j.molcel.2020.10.037_bib16","author":"DeLano"},{"key":"10.1016\/j.molcel.2020.10.037_bib17","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nrn1785","article-title":"Pathways modulating neural KCNQ\/M (Kv7) potassium channels","volume":"6","author":"Delmas","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.molcel.2020.10.037_bib18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0014-2999(02)01287-6","article-title":"Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352","volume":"437","author":"Dupuis","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib19","doi-asserted-by":"crossref","first-page":"22749","DOI":"10.1074\/jbc.M114.589796","article-title":"Novel Kv7.1-phosphatidylinositol 4,5-bisphosphate interaction sites uncovered by charge neutralization scanning","volume":"289","author":"Eckey","year":"2014","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib20","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.molcel.2020.10.037_bib21","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1517\/14740338.2013.823399","article-title":"Safety profile of two novel antiepileptic agents approved for the treatment of refractory partial seizures: ezogabine (retigabine) and perampanel","volume":"12","author":"Faulkner","year":"2013","journal-title":"Expert Opin. Drug Saf."},{"key":"10.1016\/j.molcel.2020.10.037_bib22","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/0091-3057(94)90267-4","article-title":"Linopirdine (DuP 996) improves performance in several tests of learning and memory by modulation\u00a0of cholinergic neurotransmission","volume":"49","author":"Fontana","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.molcel.2020.10.037_bib23","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1212\/WNL.0b013e3182194bd3","article-title":"Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy","volume":"76","author":"French","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.molcel.2020.10.037_bib98","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1038\/nprot.2014.173","article-title":"Screening and large-scale expression of membrane proteins in mammalian cells for structural studies","volume":"9","author":"Goehring","year":"2014","journal-title":"Nat Protoc"},{"key":"10.1016\/j.molcel.2020.10.037_bib24","doi-asserted-by":"crossref","first-page":"e06980","DOI":"10.7554\/eLife.06980","article-title":"Measuring the optimal exposure for single particle cryo-EM using a 2.6\u00a0\u00c5 reconstruction of rotavirus VP6","volume":"4","author":"Grant","year":"2015","journal-title":"eLife"},{"key":"10.1016\/j.molcel.2020.10.037_bib25","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00018-016-2359-y","article-title":"Modulation of Kv7 channels and excitability in the brain","volume":"74","author":"Greene","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.molcel.2020.10.037_bib26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1124\/jpet.117.241679","article-title":"XE991 and linopirdine are state-dependent inhibitors for Kv7\/KCNQ channels that favor activated single subunits","volume":"362","author":"Greene","year":"2017","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.molcel.2020.10.037_bib27","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1517\/14728222.12.5.565","article-title":"The therapeutic potential of neuronal K V 7 (KCNQ) channel modulators: an update","volume":"12","author":"Gribkoff","year":"2008","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.molcel.2020.10.037_bib28","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1528-1167.2011.03365.x","article-title":"The mechanism of action of retigabine (ezogabine), a first-in-class K+ channel opener for the treatment of epilepsy","volume":"53","author":"Gunthorpe","year":"2012","journal-title":"Epilepsia"},{"key":"10.1016\/j.molcel.2020.10.037_bib29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1124\/pr.57.4.10","article-title":"International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels","volume":"57","author":"Gutman","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.molcel.2020.10.037_bib30","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature10370","article-title":"Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2","volume":"477","author":"Hansen","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.10.037_bib31","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1113\/jphysiol.2007.148304","article-title":"Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications","volume":"586","author":"Hernandez","year":"2008","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1113\/jphysiol.1945.sp004114","article-title":"Resting and action potentials in single nerve fibres","volume":"104","author":"Hodgkin","year":"1945","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib33","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1113\/jphysiol.1952.sp004764","article-title":"A quantitative description of membrane current and its application to conduction and excitation in nerve","volume":"117","author":"Hodgkin","year":"1952","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib34","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1113\/jphysiol.2011.224212","article-title":"Voltage-gated potassium channels and the diversity of electrical signalling","volume":"590","author":"Jan","year":"2012","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/35036198","article-title":"Neuronal KCNQ potassium channels: physiology and role in disease","volume":"1","author":"Jentsch","year":"2000","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.molcel.2020.10.037_bib36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.cell.2019.11.041","article-title":"Structure of the cardiac sodium channel","volume":"180","author":"Jiang","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.10.037_bib37","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1124\/jpet.108.147785","article-title":"KCNQ modulators reveal a key role for KCNQ potassium channels in regulating the tone of rat pulmonary artery smooth muscle","volume":"329","author":"Joshi","year":"2009","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.molcel.2020.10.037_bib38","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.hrthm.2009.05.021","article-title":"Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test","volume":"6","author":"Kapplinger","year":"2009","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.molcel.2020.10.037_bib39","doi-asserted-by":"crossref","first-page":"7474","DOI":"10.1038\/srep07474","article-title":"PIP2-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6","volume":"5","author":"Kasimova","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.molcel.2020.10.037_bib40","doi-asserted-by":"crossref","first-page":"8116","DOI":"10.1038\/ncomms9116","article-title":"Atomic basis for therapeutic activation of neuronal potassium channels","volume":"6","author":"Kim","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.molcel.2020.10.037_bib41","doi-asserted-by":"crossref","first-page":"e18722","DOI":"10.7554\/eLife.18722","article-title":"Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2","volume":"5","author":"Kimanius","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.molcel.2020.10.037_bib42","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0092-8674(00)80556-5","article-title":"KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness","volume":"96","author":"Kubisch","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.10.037_bib43","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1124\/mol.115.103200","article-title":"Synthesis and evaluation of potent KCNQ2\/3-specific channel activators","volume":"89","author":"Kumar","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib44","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1124\/mol.108.052282","article-title":"Refinement of the binding site and mode of action of the anticonvulsant retigabine on KCNQ K+ channels","volume":"75","author":"Lange","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ajhg.2017.05.016","article-title":"Loss-of-function and gain-of-function mutations in KCNQ5 cause intellectual disability or epileptic encephalopathy","volume":"101","author":"Lehman","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.molcel.2020.10.037_bib46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jsb.2005.01.002","article-title":"Automated acquisition of cryo-electron micrographs for single particle reconstruction on an FEI Tecnai electron microscope","volume":"150","author":"Lei","year":"2005","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib47","article-title":"Structural basis for pore blockade of the human cardiac sodium channel Nav1.5 by tetrodotoxin and quinidine","author":"Li","year":"2020","journal-title":"bioRxiv"},{"issue":"W1","key":"10.1016\/j.molcel.2020.10.037_bib48","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI search and sequence analysis tools APIs in 2019","volume":"47","author":"Madeira","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.molcel.2020.10.037_bib49","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.coph.2007.10.003","article-title":"Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs","volume":"8","author":"Miceli","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib50","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1001\/jama.294.23.2975","article-title":"Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice","volume":"294","author":"Napolitano","year":"2005","journal-title":"JAMA"},{"key":"10.1016\/j.molcel.2020.10.037_bib51","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1021\/acs.jmedchem.9b00796","article-title":"Synthesis and pharmacological characterization of conformationally restricted retigabine analogues as novel neuronal Kv7 channel activators","volume":"63","author":"Ostacolo","year":"2020","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib52","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1126\/science.aaw2999","article-title":"Molecular basis for pore blockade of human Na+ channel Nav1.2 by the \u03bc-conotoxin KIIIA","volume":"363","author":"Pan","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.10.037_bib53","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1113\/jphysiol.2007.148254","article-title":"Kv7.1 (KCNQ1) properties and channelopathies","volume":"586","author":"Peroz","year":"2008","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib54","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib55","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.nurt.2006.11.012","article-title":"Retigabine","volume":"4","author":"Porter","year":"2007","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.molcel.2020.10.037_bib56","doi-asserted-by":"crossref","first-page":"C473","DOI":"10.1152\/ajpcell.2001.280.3.C473","article-title":"Effects of KCNQ channel blockers on K(+) currents in vestibular hair cells","volume":"280","author":"Rennie","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(01)00116-4","article-title":"KCNQ potassium channels: physiology, pathophysiology, and pharmacology","volume":"90","author":"Robbins","year":"2001","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.molcel.2020.10.037_bib58","doi-asserted-by":"crossref","first-page":"W320-4","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering key features in protein structures with the new ENDscript server","volume":"42","author":"Robert","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.molcel.2020.10.037_bib59","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s11910-008-0053-7","article-title":"New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7\/KCNQ\/M potassium channels","volume":"8","author":"Rogawski","year":"2008","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"10.1016\/j.molcel.2020.10.037_bib60","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.jmb.2003.07.013","article-title":"Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy","volume":"333","author":"Rosenthal","year":"2003","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0014-2999(97)01249-1","article-title":"The new anticonvulsant retigabine (D-23129) acts as an opener of K+ channels in neuronal cells","volume":"336","author":"Rundfeldt","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib62","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1523\/JNEUROSCI.0128-05.2005","article-title":"Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine","volume":"25","author":"Schenzer","year":"2005","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.molcel.2020.10.037_bib63","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","article-title":"RELION: implementation of a Bayesian approach to cryo-EM structure determination","volume":"180","author":"Scheres","year":"2012","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib64","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jsb.2014.11.010","article-title":"Semi-automated selection of cryo-EM particles in RELION-1.3","volume":"189","author":"Scheres","year":"2015","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib65","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0022-3565(24)37644-X","article-title":"Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons","volume":"286","author":"Schnee","year":"1998","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.molcel.2020.10.037_bib66","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/25367","article-title":"Moderate loss of function of cyclic-AMP-modulated KCNQ2\/KCNQ3 K+ channels causes epilepsy","volume":"396","author":"Schroeder","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.10.037_bib67","doi-asserted-by":"crossref","first-page":"eaau2596","DOI":"10.1126\/science.aau2596","article-title":"Structural basis for the modulation of voltage-gated sodium channels by animal toxins","volume":"362","author":"Shen","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.10.037_bib68","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00232-020-00113-6","article-title":"Molecular mechanisms and structural basis of retigabine analogues in regulating KCNQ2 channel","volume":"253","author":"Shi","year":"2020","journal-title":"J.\u00a0Membr. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib69","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng0198-25","article-title":"A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns","volume":"18","author":"Singh","year":"1998","journal-title":"Nat. Genet."},{"key":"10.1016\/j.molcel.2020.10.037_bib70","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1038\/s41467-018-04828-y","article-title":"Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB","volume":"9","author":"Singh","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.molcel.2020.10.037_bib71","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0263-7855(97)00009-X","article-title":"HOLE: a program for the analysis of the pore dimensions of ion channel structural models","volume":"14","author":"Smart","year":"1996","journal-title":"J.\u00a0Mol. Graph."},{"key":"10.1016\/j.molcel.2020.10.037_bib72","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0896-6273(02)00790-0","article-title":"Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis","volume":"35","author":"Suh","year":"2002","journal-title":"Neuron"},{"key":"10.1016\/j.molcel.2020.10.037_bib73","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1126\/science.1131163","article-title":"Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels","volume":"314","author":"Suh","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.10.037_bib74","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2017.05.019","article-title":"Cryo-EM structure of a KCNQ1\/CaM complex reveals insights into congenital long QT syndrome","volume":"169","author":"Sun","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.10.037_bib75","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.cell.2019.12.003","article-title":"Structural basis of human KCNQ1 modulation and gating","volume":"180","author":"Sun","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.10.037_bib76","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1039\/C9OB00511K","article-title":"Flupirtine and retigabine as templates for ligand-based drug design of KV7.2\/3 activators","volume":"17","author":"Surur","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib77","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jmb.2008.06.085","article-title":"Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers","volume":"382","author":"Tao","year":"2008","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib78","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1523\/JNEUROSCI.21-15-05535.2001","article-title":"Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine","volume":"21","author":"Tatulian","year":"2001","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.molcel.2020.10.037_bib79","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7554\/eLife.53901","article-title":"Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state","volume":"9","author":"Taylor","year":"2020","journal-title":"eLife"},{"key":"10.1016\/j.molcel.2020.10.037_bib80","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1074\/jbc.M110.153551","article-title":"Characterization of a binding site for anionic phospholipids on KCNQ1","volume":"286","author":"Thomas","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib81","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/1096-8628(20000731)93:3<184::AID-AJMG4>3.0.CO;2-5","article-title":"Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region","volume":"93","author":"Van Hauwe","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.molcel.2020.10.037_bib82","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1126\/science.282.5395.1890","article-title":"KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel","volume":"282","author":"Wang","year":"1998","journal-title":"Science"},{"issue":"W1","key":"10.1016\/j.molcel.2020.10.037_bib83","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.molcel.2020.10.037_bib84","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1085\/jgp.201010408","article-title":"State-dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation","volume":"135","author":"Wu","year":"2010","journal-title":"J.\u00a0Gen. Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib85","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1124\/mol.104.010793","article-title":"The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate","volume":"67","author":"Wuttke","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib86","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1161\/CIRCEP.109.850149","article-title":"Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndrome","volume":"2","author":"Yang","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib87","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/sj.bjp.0706342","article-title":"Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells","volume":"146","author":"Yeung","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.molcel.2020.10.037_bib88","doi-asserted-by":"crossref","first-page":"28545","DOI":"10.1074\/jbc.M204130200","article-title":"The identification and characterization of a noncontinuous calmodulin-binding site in noninactivating voltage-dependent KCNQ potassium channels","volume":"277","author":"Yus-Najera","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.molcel.2020.10.037_bib89","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0022-3565(24)37471-3","article-title":"Two new potent neurotransmitter release enhancers, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4-pyridinylmethyl)-9(10H)-anthracenone: comparison to linopirdine","volume":"285","author":"Zaczek","year":"1998","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.molcel.2020.10.037_bib90","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fphys.2014.00195","article-title":"PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating","volume":"5","author":"Zaydman","year":"2014","journal-title":"Front. Physiol."},{"key":"10.1016\/j.molcel.2020.10.037_bib91","doi-asserted-by":"crossref","first-page":"13180","DOI":"10.1073\/pnas.1305167110","article-title":"Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening","volume":"110","author":"Zaydman","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.molcel.2020.10.037_bib92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsb.2015.11.003","article-title":"Gctf: Real-time CTF determination and correction","volume":"193","author":"Zhang","year":"2016","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.molcel.2020.10.037_bib93","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/S0896-6273(03)00125-9","article-title":"PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents","volume":"37","author":"Zhang","year":"2003","journal-title":"Neuron"},{"key":"10.1016\/j.molcel.2020.10.037_bib94","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nature11054","article-title":"Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel","volume":"486","author":"Zhang","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.10.037_bib95","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.cell.2019.04.043","article-title":"Molecular basis for ligand modulation of a mammalian voltage-gated Ca(2+) channel","volume":"177","author":"Zhao","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.10.037_bib96","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.pain.2012.12.005","article-title":"Suppression of KCNQ\/M (Kv7) potassium channels in dorsal root ganglion neurons contributes to the development of bone cancer pain in a rat model","volume":"154","author":"Zheng","year":"2013","journal-title":"Pain"},{"key":"10.1016\/j.molcel.2020.10.037_bib97","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.4193","article-title":"MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy","volume":"14","author":"Zheng","year":"2017","journal-title":"Nat. Methods"}],"container-title":["Molecular Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1097276520307711?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1097276520307711?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:36:01Z","timestamp":1761093361000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1097276520307711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":98,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S1097276520307711"],"URL":"https:\/\/doi.org\/10.1016\/j.molcel.2020.10.037","relation":{},"ISSN":["1097-2765"],"issn-type":[{"value":"1097-2765","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs","name":"articletitle","label":"Article Title"},{"value":"Molecular Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molcel.2020.10.037","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}