{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:09:24Z","timestamp":1782259764022,"version":"3.54.5"},"reference-count":52,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1203100"],"award-info":[{"award-number":["2022YFF1203100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Advanced Interdisciplinary Science and Biomedicine of IHM","award":["QYZD20220006"],"award-info":[{"award-number":["QYZD20220006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401024"],"award-info":[{"award-number":["32401024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China"},{"DOI":"10.13039\/501100009076","name":"University of Science and Technology of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2308085QC77"],"award-info":[{"award-number":["2308085QC77"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["WK9100000070"],"award-info":[{"award-number":["WK9100000070"]}],"id":[{"id":"10.13039\/501100012226","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":[[2025,7]]},"DOI":"10.1016\/j.jbc.2025.110348","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T19:09:31Z","timestamp":1749236971000},"page":"110348","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular mechanism of antagonist recognition and regulation of the \u03b11A-adrenoceptor"],"prefix":"10.1016","volume":"301","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4165-2085","authenticated-orcid":false,"given":"Sisi","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-2276","authenticated-orcid":false,"given":"Haizhan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyong","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2025.110348_bib1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12964-021-00755-6","article-title":"Role of \u03b1- and \u03b2-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease","volume":"19","author":"Archer","year":"2021","journal-title":"Cell. Commun. Signal."},{"key":"10.1016\/j.jbc.2025.110348_bib2","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1152\/ajplegacy.1948.153.3.586","article-title":"A study of the adrenotropic receptors","volume":"153","author":"Ahlquist","year":"1948","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.jbc.2025.110348_bib3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0031-6997(25)06780-8","article-title":"International union of pharmacology nomenclature of adrenoceptors","volume":"46","author":"Bylund","year":"1994","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.jbc.2025.110348_bib4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1161\/01.RES.78.5.737","article-title":"Alpha 1-adrenergic receptor subtypes. Molecular structure, function, and signaling","volume":"78","author":"Graham","year":"1996","journal-title":"Circ. Res."},{"key":"10.1016\/j.jbc.2025.110348_bib5","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1111\/bph.14617","article-title":"Updates in the function and regulation of alpha(1) -adrenoceptors","volume":"176","author":"Akinaga","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2025.110348_bib6","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.3390\/ijms24044188","article-title":"alpha(1)-Adrenergic receptors: insights into potential therapeutic opportunities for COVID-19, heart failure, and Alzheimer's disease","volume":"24","author":"Perez","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jbc.2025.110348_bib7","series-title":"Alpha 1 adrenergic receptor antagonists in LiverTox: Clinical and research Information on drug-induced liver injury","year":"2012"},{"key":"10.1016\/j.jbc.2025.110348_bib8","series-title":"Goodman and Gilman's Manual of Pharmacology and Therapeutics, 2e","article-title":"Treatment of myocardial ischemia and hypertension","author":"Hilal-Dandan","year":"2016"},{"key":"10.1016\/j.jbc.2025.110348_bib9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1161\/01.HYP.0000086521.95630.5A","article-title":"Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)","volume":"42","year":"2003","journal-title":"Hypertension"},{"key":"10.1016\/j.jbc.2025.110348_bib10","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1001\/jama.2013.284427","article-title":"2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)","volume":"311","author":"James","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.jbc.2025.110348_bib11","first-page":"181","article-title":"Alpha blockers for the treatment of benign prostatic hyperplasia","volume":"9","author":"Lepor","year":"2007","journal-title":"Rev. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib12","first-page":"255","article-title":"The use of alpha-adrenergic blockers in benign prostatic obstruction","volume":"48","author":"Caine","year":"1976","journal-title":"Br. J. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib13","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1464-410X.1978.tb06210.x","article-title":"A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction","volume":"50","author":"Caine","year":"1978","journal-title":"Br. J. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib14","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1464-410X.1987.tb04950.x","article-title":"Prazosin in the treatment of prostatic obstruction. A placebo-controlled study","volume":"60","author":"Kirby","year":"1987","journal-title":"Br. J. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1046\/j.1464-410X.1998.00747.x","article-title":"Terazosin in benign prostatic hyperplasia: effects on blood pressure in normotensive and hypertensive men","volume":"82","author":"Kirby","year":"1998","journal-title":"Br. J. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib16","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0090-4295(99)80191-5","article-title":"Doxazosin in benign prostatic hyperplasia: effects on blood pressure and urinary flow in normotensive and hypertensive men","volume":"46","author":"Kirby","year":"1995","journal-title":"Urology"},{"key":"10.1016\/j.jbc.2025.110348_bib17","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1159\/000052361","article-title":"Efficacy and safety of a new prolonged release formulation of alfuzosin 10 mg once daily versus alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. ALFORTI Study Group","volume":"37","author":"van Kerrebroeck","year":"2000","journal-title":"Eur. Urol."},{"key":"10.1016\/j.jbc.2025.110348_bib18","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0090-4295(01)01448-0","article-title":"Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial","volume":"58","author":"Roehrborn","year":"2001","journal-title":"Urology"},{"key":"10.1016\/j.jbc.2025.110348_bib19","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/j.1476-5381.1996.tb15480.x","article-title":"Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies","volume":"118","author":"Kenny","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2025.110348_bib20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0026-895X(25)10156-9","article-title":"The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype","volume":"45","author":"Forray","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.jbc.2025.110348_bib21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2147\/CIA.S13803","article-title":"Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia","volume":"6","author":"Yoshida","year":"2011","journal-title":"Clin. Interv. Aging."},{"key":"10.1016\/j.jbc.2025.110348_bib22","first-page":"209","article-title":"[Alpha1-adrenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213)]","volume":"126","author":"Tatemichi","year":"2006","journal-title":"Yakugaku. Zasshi."},{"key":"10.1016\/j.jbc.2025.110348_bib23","first-page":"3","article-title":"Silodosin (Rapaflo) for benign prostatic hyperplasia","volume":"51","year":"2009","journal-title":"Med. Lett. Drugs. Ther."},{"key":"10.1016\/j.jbc.2025.110348_bib24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-020-00435-w","article-title":"G protein-coupled receptors: structure- and function-based drug discovery","volume":"6","author":"Yang","year":"2021","journal-title":"Signal. Transduct. Target. Ther."},{"key":"10.1016\/j.jbc.2025.110348_bib25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cell.2020.03.003","article-title":"Impact of GPCR structures on drug discovery","volume":"181","author":"Congreve","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2025.110348_bib26","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1021\/acs.jmedchem.9b01560","article-title":"Docking finds GPCR ligands in dark chemical matter","volume":"63","author":"Ballante","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jbc.2025.110348_bib27","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1038\/s41467-023-39310-x","article-title":"Structural basis of \u03b11A-adrenergic receptor activation and recognition by an extracellular nanobody","volume":"14","author":"Toyoda","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2025.110348_bib28","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1038\/s41467-023-40524-2","article-title":"Structural basis of agonist specificity of \u03b11A-adrenergic receptor","volume":"14","author":"Su","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2025.110348_bib29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41589-023-01389-0","article-title":"A method for structure determination of GPCRs in various states","volume":"20","author":"Guo","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110348_bib30","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.50279","article-title":"Common activation mechanism of class A GPCRs","volume":"8","author":"Zhou","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2025.110348_bib31","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature23652","article-title":"Mechanism of intracellular allosteric \u03b2(2)AR antagonist revealed by X-ray crystal structure","volume":"548","author":"Liu","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2025.110348_bib32","series-title":"Methods in Neurosciences","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/S1043-9471(05)80049-7","article-title":"[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors","author":"Ballesteros","year":"1995"},{"key":"10.1016\/j.jbc.2025.110348_bib33","doi-asserted-by":"crossref","first-page":"D1516","DOI":"10.1093\/nar\/gkae1059","article-title":"PubChem 2025 update","volume":"53","author":"Kim","year":"2025","journal-title":"Nucleic. Acids. Res."},{"key":"10.1016\/j.jbc.2025.110348_bib52","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: the DrugBank Knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2025.110348_bib34","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1073\/pnas.84.13.4384","article-title":"Identification of residues required for ligand binding to the beta-adrenergic receptor","volume":"84","author":"Strader","year":"1987","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2025.110348_bib35","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.1021\/bi972733a","article-title":"Alpha 1-adrenergic receptor subtype determinants for 4-piperidyl oxazole antagonists","volume":"37","author":"Hamaguchi","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2025.110348_bib36","doi-asserted-by":"crossref","first-page":"14312","DOI":"10.1021\/bi961024e","article-title":"Phenylalanine in the second membrane-spanning domain of alpha 1A-adrenergic receptor determines subtype selectivity of dihydropyridine antagonists","volume":"35","author":"Hamaguchi","year":"1996","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2025.110348_bib37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pbiomolbio.2020.07.009","article-title":"Amorphous nickel titanium alloy film: a new choice for cryo electron microscopy sample preparation","volume":"156","author":"Huang","year":"2020","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"10.1016\/j.jbc.2025.110348_bib50","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.2025.110348_bib38","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.2025.110348_bib39","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1107\/S2059798316019276","article-title":"A pipeline approach to single-particle processing in RELION","volume":"73","author":"Fernandez-Leiro","year":"2017","journal-title":"Acta. Crystallogr. D. Struct. Biol."},{"key":"10.1016\/j.jbc.2025.110348_bib49","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. Struct. Biol."},{"key":"10.1016\/j.jbc.2025.110348_bib48","doi-asserted-by":"crossref","first-page":"7822","DOI":"10.1038\/s41467-023-43555-x","article-title":"A minority of final stacks yields superior amplitude in single-particle cryo-EM","volume":"14","author":"Zhu","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2025.110348_bib40","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. Comput. Chem."},{"key":"10.1016\/j.jbc.2025.110348_bib41","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.jbc.2025.110348_bib42","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.jbc.2025.110348_bib51","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"10.1016\/j.jbc.2025.110348_bib43","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: all-atom structure validation for macromolecular crystallography","volume":"66","author":"Chen","year":"2010","journal-title":"Acta. Crystallogr. D. Biol. Crystallogr."},{"key":"10.1016\/j.jbc.2025.110348_bib44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/pro.3235","article-title":"UCSF ChimeraX: meeting modern challenges in visualization and analysis","volume":"27","author":"Goddard","year":"2018","journal-title":"Protein. Sci."},{"key":"10.1016\/j.jbc.2025.110348_bib45","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.cell.2019.04.044","article-title":"Illuminating G-protein-coupling selectivity of GPCRs","volume":"177","author":"Inoue","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2025.110348_bib46","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1080\/01621459.1955.10501294","article-title":"A multiple comparison procedure for comparing several treatments with a control","volume":"50","author":"Dunnett","year":"1955","journal-title":"J. Am. Stat. Assoc."},{"key":"10.1016\/j.jbc.2025.110348_bib47","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1124\/jpet.119.264143","article-title":"New author guidelines for displaying data and reporting data analysis and statistical methods in experimental biology","volume":"372","author":"Michel","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825021982?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825021982?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T15:40:31Z","timestamp":1761147631000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925825021982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["S0021925825021982"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2025.110348","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Molecular mechanism of antagonist recognition and regulation of the \u03b11A-adrenoceptor","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2025.110348","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"110348"}}