Downloads: 568

Files in This Item:
File Description SizeFormat 
nature10753.pdf607.63 kBAdobe PDFView/Open
Full metadata record
DC FieldValueLanguage
dc.contributor.authorHaga, Kazukoja
dc.contributor.authorKruse, Andrew C.ja
dc.contributor.authorAsada, Hidetsuguja
dc.contributor.authorYurugi-Kobayashi, Takamija
dc.contributor.authorShiroishi, Mitsunorija
dc.contributor.authorZhang, Chengja
dc.contributor.authorWeis, William I.ja
dc.contributor.authorOkada, Tetsujija
dc.contributor.authorKobilka, Brian K.ja
dc.contributor.authorHaga, Tatsuyaja
dc.contributor.authorKobayashi, Takuyaja
dc.contributor.alternative小林, 拓也ja
dc.date.accessioned2012-01-27T05:57:33Z-
dc.date.available2012-01-27T05:57:33Z-
dc.date.issued2012-01-25ja
dc.identifier.issn0028-0836ja
dc.identifier.urihttp://hdl.handle.net/2433/152410-
dc.description認知症や心機能の抑制に関係する受容体の立体構造を世界で初めて解明-より効果的で副作用のない治療薬の探索・設計が可能に-. 京都大学プレスリリース.2012-01-26.ja
dc.description.abstractThe parasympathetic branch of the autonomic nervous system regulates the activity ofmultiple organ systems.Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves1–5. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassiumchannels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands.Herewe report the structure of the antagonistbound humanM2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.ja
dc.format.mimetypeapplication/pdfja
dc.language.isoengja
dc.publisherNature Publishing Groupja
dc.rights©2012 Macmillan Publishers Limited. All rights reservedja
dc.rights許諾条件により本文は2012-07-25に公開.ja
dc.rightsこの論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.ja
dc.titleStructure of the human M2 muscarinic acetylcholine receptor bound to an antagonistja
dc.identifier.urlhttp://www.nature.com/nature/journal/vaop/ncurrent/full/nature10753.htmlja
dc.type.niitypeJournal Articleja
dc.identifier.jtitleNatureja
dc.identifier.volume482ja
dc.identifier.issue7386ja
dc.identifier.spage547ja
dc.identifier.epage551ja
dc.relation.doi10.1038/nature10753ja
dc.textversionauthorja
dc.startdate.bitstreamsavailable2012-07-25ja
dc.relation.urlhttps://www.kyoto-u.ac.jp/static/ja/news_data/h/h1/news6/2011/120126_1.htmja
Appears in Collections:Journal Articles

Show simple item record

Export to RefWorks


Export Format: 


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.