{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:55:58Z","timestamp":1787684158507,"version":"build-2784847793"},"reference-count":34,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006975","name":"Indiana Clinical and Translational Sciences Institute","doi-asserted-by":"publisher","award":["UM1TR004402"],"award-info":[{"award-number":["UM1TR004402"]}],"id":[{"id":"10.13039\/100006975","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012752","name":"Elanco Animal Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.jbc.2024.108109","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:29:33Z","timestamp":1734568173000},"page":"108109","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist"],"prefix":"10.1016","volume":"301","author":[{"given":"Trung","family":"Thach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KanagaVijayan","family":"Dhanabalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0210-9301","authenticated-orcid":false,"given":"Prajwal Prabhakarrao","family":"Nandekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Stauffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iring","family":"Heisler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Alvarado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2762-934X","authenticated-orcid":false,"given":"Jonathan","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-190X","authenticated-orcid":false,"given":"Ramaswamy","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2024.108109_bib1","doi-asserted-by":"crossref","first-page":"653561","DOI":"10.3389\/fphar.2021.653561","article-title":"P2X3 receptor ligands: structural features and potential therapeutic applications","volume":"12","author":"Spinaci","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jbc.2024.108109_bib2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nature04886","article-title":"P2X receptors as cell-surface ATP sensors in health and disease","volume":"442","author":"Khakh","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2024.108109_bib3","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/prot.26302","article-title":"Recent progress in the structural biology of P2X receptors","volume":"90","author":"Sheng","year":"2022","journal-title":"Proteins"},{"key":"10.1016\/j.jbc.2024.108109_bib4","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1126\/science.1118435","article-title":"ATP signaling is crucial for communication from taste buds to gustatory nerves","volume":"310","author":"Finger","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.jbc.2024.108109_bib5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fncel.2013.00267","article-title":"The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders","volume":"7","author":"Ford","year":"2013","journal-title":"Front. Cell Neurosci."},{"key":"10.1016\/j.jbc.2024.108109_bib6","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/S0140-6736(14)61255-1","article-title":"P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study","volume":"385","author":"Abdulqawi","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.jbc.2024.108109_bib7","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1073\/pnas.1800907115","article-title":"Druggable negative allosteric site of P2X3 receptors","volume":"115","author":"Wang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2024.108109_bib8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pupt.2019.03.007","article-title":"BLU-5937: a selective P2X3 antagonist with potent anti-tussive effect and no taste alteration","volume":"56","author":"Garceau","year":"2019","journal-title":"Pulm. Pharmacol. Ther."},{"key":"10.1016\/j.jbc.2024.108109_bib9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11302-021-09790-x","article-title":"Structural basis for the functional properties of the P2X7 receptor for extracellular ATP","volume":"17","author":"Jiang","year":"2021","journal-title":"Purinergic Signal."},{"key":"10.1016\/j.jbc.2024.108109_bib10","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nature19367","article-title":"X-ray structures define human P2X3 receptor gating cycle and antagonist action","volume":"538","author":"Mansoor","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2024.108109_bib11","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/s41467-017-00887-9","article-title":"Structural insights into the competitive inhibition of the ATP-gated P2X receptor channel","volume":"8","author":"Kasuya","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2024.108109_bib12","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1038\/s41467-023-42164-y","article-title":"Structural insights into the allosteric inhibition of P2X4 receptors","volume":"14","author":"Shen","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2024.108109_bib13","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.34085","article-title":"The Peptidisc, a simple method for stabilizing membrane proteins in detergent-free solution","volume":"7","author":"Carlson","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2024.108109_bib14","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.53530","article-title":"New approach for membrane protein reconstitution into peptidiscs and basis for their adaptability to different proteins","volume":"9","author":"Angiulli","year":"2020","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2024.108109_bib15","article-title":"Cryo-EM structure of the trehalose monomycolate transporter, MmpL3, reconstituted into peptidiscs","volume":"6","author":"Couston","year":"2023","journal-title":"Curr. Res. Struct. Biol."},{"key":"10.1016\/j.jbc.2024.108109_bib16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/bioinformatics\/19.1.163","article-title":"ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information","volume":"19","author":"Glaser","year":"2003","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jbc.2024.108109_bib17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1182\/blood-2012-01-406496","article-title":"Immunoregulation through extracellular nucleotides","volume":"120","author":"Vitiello","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.jbc.2024.108109_bib18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11302-011-9271-6","article-title":"In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization","volume":"8","author":"Ford","year":"2012","journal-title":"Purinergic Signal."},{"key":"10.1016\/j.jbc.2024.108109_bib19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jsb.2005.03.010","article-title":"Automated molecular microscopy: the new Leginon system","volume":"151","author":"Suloway","year":"2005","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.jbc.2024.108109_bib20","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"},{"key":"10.1016\/j.jbc.2024.108109_bib21","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.jbc.2024.108109_bib22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jsb.2009.01.004","article-title":"DoG Picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy","volume":"166","author":"Voss","year":"2009","journal-title":"J.\u00a0Struct. Biol."},{"key":"10.1016\/j.jbc.2024.108109_bib23","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nmeth.4169","article-title":"cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination","volume":"14","author":"Punjani","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2024.108109_bib24","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41592-020-00990-8","article-title":"Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction","volume":"17","author":"Punjani","year":"2020","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2024.108109_bib25","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.jbc.2024.108109_bib26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1107\/S2059798318006551","article-title":"Real-space refinement in PHENIX for cryo-EM and crystallography","volume":"74","author":"Afonine","year":"2018","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"10.1016\/j.jbc.2024.108109_bib27","series-title":"The PyMOL Molecular Graphics System","author":"DeLano","year":"2002"},{"key":"10.1016\/j.jbc.2024.108109_bib28","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"10.1016\/j.jbc.2024.108109_bib29","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2024.108109_bib30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10858-015-9969-9","article-title":"MolProbity for the masses\u2013of data","volume":"63","author":"Chen","year":"2015","journal-title":"J.\u00a0Biomol. NMR"},{"key":"10.1016\/j.jbc.2024.108109_bib31","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. Graphics"},{"key":"10.1016\/j.jbc.2024.108109_bib32","doi-asserted-by":"crossref","first-page":"W368","DOI":"10.1093\/nar\/gky309","article-title":"MOLEonline: a web-based tool for analyzing channels, tunnels and pores (2018 update)","volume":"46","author":"Pravda","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2024.108109_bib33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J.\u00a0Chem. Theor. Comput."},{"key":"10.1016\/j.jbc.2024.108109_bib34","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1021\/acs.jctc.3c00044","article-title":"Epik: pKa and protonation state prediction through machine learning","volume":"19","author":"Johnston","year":"2023","journal-title":"J.\u00a0Chem. Theor. Comput."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925824026115?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925824026115?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:20:40Z","timestamp":1740378040000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925824026115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["S0021925824026115"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2024.108109","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2024.108109","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"108109"}}