[English] 日本語
Yorodumi
- PDB-6tos: Crystal structure of the Orexin-1 receptor in complex with GSK1059865 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6tos
TitleCrystal structure of the Orexin-1 receptor in complex with GSK1059865
ComponentsOrexin receptor type 1
KeywordsMEMBRANE PROTEIN / 7TM / GPCR
Function / homology
Function and homology information


orexin receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / feeding behavior / peptide hormone binding / neuropeptide signaling pathway / cellular response to hormone stimulus / regulation of cytosolic calcium ion concentration / G protein-coupled receptor activity / peptide binding / G alpha (q) signalling events ...orexin receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / feeding behavior / peptide hormone binding / neuropeptide signaling pathway / cellular response to hormone stimulus / regulation of cytosolic calcium ion concentration / G protein-coupled receptor activity / peptide binding / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of ERK1 and ERK2 cascade / synapse / plasma membrane
Similarity search - Function
Orexin/Hypocretin receptor type 1 / Orexin receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
CITRIC ACID / Chem-NRE / Chem-PGW / Orexin/Hypocretin receptor type 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.13 Å
AuthorsRappas, M. / Ali, A. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. ...Rappas, M. / Ali, A. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / Mason, J.S. / Mould, R. / Patel, J.C. / Tehan, B.G. / Weir, M. / Christopher, J.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA)R01DA039553 United States
CitationJournal: J.Med.Chem. / Year: 2020
Title: Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
Authors: Rappas, M. / Ali, A.A.E. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / ...Authors: Rappas, M. / Ali, A.A.E. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / Mason, J.S. / Mould, R. / Patel, J.C. / Tehan, B.G. / Weir, M. / Christopher, J.A.
History
DepositionDec 11, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 15, 2020Provider: repository / Type: Initial release
Revision 1.1Jan 29, 2020Group: Database references / Category: citation / citation_author
Item: _citation.title / _citation.year / _citation_author.name
Revision 1.2Mar 11, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Jul 29, 2020Group: Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_entity_nonpoly / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.4Jan 24, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Orexin receptor type 1
B: Orexin receptor type 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)87,95041
Polymers76,2662
Non-polymers11,68439
Water2,720151
1
A: Orexin receptor type 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,06420
Polymers38,1331
Non-polymers4,93119
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Orexin receptor type 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,88621
Polymers38,1331
Non-polymers6,75320
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)59.692, 146.19, 71.508
Angle α, β, γ (deg.)90, 112.43, 90
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein / Sugars , 2 types, 29 molecules AB

#1: Protein Orexin receptor type 1 / Ox1R / Hypocretin receptor type 1


Mass: 38132.852 Da / Num. of mol.: 2
Mutation: E46A I85L V95A R162L N194A L198A Y211A L304V C339A C375W C376W
Source method: isolated from a genetically manipulated source
Details: GSK1059865 bound in the orthosteric site / Source: (gene. exp.) Homo sapiens (human) / Gene: HCRTR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O43613
#6: Sugar...
ChemComp-SOG / octyl 1-thio-beta-D-glucopyranoside / 2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL / 1-S-OCTYL-BETA-D-THIOGLUCOSIDE / octyl 1-thio-beta-D-glucoside / octyl 1-thio-D-glucoside / octyl 1-thio-glucoside


Type: D-saccharide / Mass: 308.434 Da / Num. of mol.: 27
Source method: isolated from a genetically manipulated source
Formula: C14H28O5S / Comment: detergent*YM

-
Non-polymers , 7 types, 163 molecules

#2: Chemical ChemComp-NRE / [(2~{S},5~{S})-2-[[(5-bromanylpyridin-2-yl)amino]methyl]-5-methyl-piperidin-1-yl]-(3-fluoranyl-2-methoxy-phenyl)methanone


Mass: 436.318 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H23BrFN3O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-PG4 / TETRAETHYLENE GLYCOL


Mass: 194.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H18O5 / Comment: precipitant*YM
#4: Chemical ChemComp-CIT / CITRIC ACID


Mass: 192.124 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C6H8O7
#5: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#7: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#8: Chemical ChemComp-PGW / (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate / 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-[Phospho-(1-glycerol)] / PHOSPHATIDYLGLYCEROL


Mass: 749.007 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C40H77O10P / Comment: phospholipid*YM
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 151 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.78 Å3/Da / Density % sol: 67.47 %
Crystal growTemperature: 284 K / Method: vapor diffusion, sitting drop / pH: 5
Details: 0.1M TRISODIUM CITRATE 50mM SODIUM CHLORIDE 50mM LITHIUM SULPHATE 15-34% PEG400
PH range: 3.0-6.5 / Temp details: Stable

-
Data collection

DiffractionMean temperature: 100 K / Ambient temp details: Stable / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.98658 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 25, 2015
RadiationMonochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98658 Å / Relative weight: 1
ReflectionResolution: 2.13→30.47 Å / Num. obs: 44881 / % possible obs: 71.1 % / Redundancy: 3.3 % / CC1/2: 0.99 / Net I/σ(I): 8.8
Reflection shellResolution: 2.13→2.25 Å / Num. unique obs: 898 / CC1/2: 0.338 / % possible all: 9.19

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
STARANISOdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6TO7

6to7


Resolution: 2.13→30.47 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.92 / SU R Cruickshank DPI: 0.232 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.222 / SU Rfree Blow DPI: 0.179 / SU Rfree Cruickshank DPI: 0.184
RfactorNum. reflection% reflectionSelection details
Rfree0.218 2197 -RANDOM
Rwork0.193 ---
obs0.194 44881 71.1 %-
Displacement parametersBiso mean: 60.1 Å2
Baniso -1Baniso -2Baniso -3
1--0.547 Å20 Å20.2493 Å2
2--0.3926 Å20 Å2
3---0.1544 Å2
Refine analyzeLuzzati coordinate error obs: 0.28 Å
Refinement stepCycle: LAST / Resolution: 2.13→30.47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4877 0 609 151 5637
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.015688HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.967718HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2048SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes831HARMONIC5
X-RAY DIFFRACTIONt_it5688HARMONIC20
X-RAY DIFFRACTIONt_nbd5SEMIHARMONIC5
X-RAY DIFFRACTIONt_chiral_improper_torsion710SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies4HARMONIC1
X-RAY DIFFRACTIONt_ideal_dist_contact6421SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion2.78
X-RAY DIFFRACTIONt_other_torsion16.41
LS refinement shellResolution: 2.13→2.25 Å
RfactorNum. reflection% reflection
Rfree0.249 29 -
Rwork0.2173 --
obs0.2184 898 9.19 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.2205-0.3552-0.57623.08561.51192.16760.04290.1811-0.01310.18110.3340.5142-0.01310.5142-0.3769-0.28270.0138-0.0409-0.0591-0.1247-0.0811-27.1257-5.504398.7271
21.2010.0475-0.23033.71770.08551.3089-0.0458-0.43710.09-0.43710.13670.08490.090.0849-0.091-0.1065-0.00750.0236-0.1654-0.0138-0.2057-32.132-28.365273.9179
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{A|*}
2X-RAY DIFFRACTION2{B|*}

+
About Yorodumi

-
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://pdbjlvh1.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

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more