[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleStructures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 815, Year 2021
Publish dateFeb 5, 2021
AuthorsChuan Hong / Noel J Byrne / Beata Zamlynny / Srivanya Tummala / Li Xiao / Jennifer M Shipman / Andrea T Partridge / Christina Minnick / Michael J Breslin / Michael T Rudd / Shawn J Stachel / Vanessa L Rada / Jeffrey C Kern / Kira A Armacost / Scott A Hollingsworth / Julie A O'Brien / Dawn L Hall / Terrence P McDonald / Corey Strickland / Alexei Brooun / Stephen M Soisson / Kaspar Hollenstein /
PubMed AbstractNarcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain's ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest ...Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain's ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OXR) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OXR agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OXR bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OXR to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OXR suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders.
External linksNat Commun / PubMed:33547286 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 3.2 Å
Structure data

23118

7l1u

EMDB-23118, PDB-7l1u:
Orexin Receptor 2 (OX2R) in Complex with G Protein and Natural Peptide-Agonist Orexin B (OxB)
Method: EM (single particle) / Resolution: 3.2 Å

23119

7l1v

EMDB-23119, PDB-7l1v:
Orexin Receptor 2 (OX2R) in Complex with G Protein and Small-Molecule Agonist Compound 1
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-XGD:
4'-methoxy-N,N-dimethyl-3'-{[3-(2-{[2-(2H-1,2,3-triazol-2-yl)benzene-1-carbonyl]amino}ethyl)phenyl]sulfamoyl}[1,1'-biphenyl]-3-carboxamide

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / Class A GPCR / Orexin receptor 2 / OX2R / Peptide agonist

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more