[English] 日本語
Yorodumi
- PDB-6xf4: Crystal structure of STING REF variant in complex with E7766 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xf4
TitleCrystal structure of STING REF variant in complex with E7766
ComponentsStimulator of interferon genes protein
KeywordsIMMUNE SYSTEM / Stimulator of interferon genes (STING) / REF variant / E7766 / Agonist / Macrocycle
Function / homology
Function and homology information


STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / serine/threonine protein kinase complex / proton channel activity / 2',3'-cyclic GMP-AMP binding / STING mediated induction of host immune responses / cyclic-di-GMP binding / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway ...STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / serine/threonine protein kinase complex / proton channel activity / 2',3'-cyclic GMP-AMP binding / STING mediated induction of host immune responses / cyclic-di-GMP binding / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / cGAS/STING signaling pathway / reticulophagy / pattern recognition receptor signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / autophagosome membrane / antiviral innate immune response / positive regulation of macroautophagy / cellular response to organic cyclic compound / autophagosome assembly / autophagosome / positive regulation of type I interferon production / cellular response to interferon-beta / signaling adaptor activity / positive regulation of defense response to virus by host / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / endoplasmic reticulum-Golgi intermediate compartment membrane / secretory granule membrane / cytoplasmic vesicle membrane / positive regulation of DNA-binding transcription factor activity / peroxisome / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / protein complex oligomerization / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / plasma membrane / cytosol
Similarity search - Function
: / Stimulator of interferon genes protein / Stimulator of interferon genes protein, C-terminal domain superfamily / Transmembrane protein 173
Similarity search - Domain/homology
Chem-V5V / Stimulator of interferon genes protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.77 Å
AuthorsChen, Y. / Wang, J.Y. / Kim, D.-S.
CitationJournal: Chemmedchem / Year: 2021
Title: E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity.
Authors: Kim, D.S. / Endo, A. / Fang, F.G. / Huang, K.C. / Bao, X. / Choi, H.W. / Majumder, U. / Shen, Y.Y. / Mathieu, S. / Zhu, X. / Sanders, K. / Noland, T. / Hao, M.H. / Chen, Y. / Wang, J.Y. / ...Authors: Kim, D.S. / Endo, A. / Fang, F.G. / Huang, K.C. / Bao, X. / Choi, H.W. / Majumder, U. / Shen, Y.Y. / Mathieu, S. / Zhu, X. / Sanders, K. / Noland, T. / Hao, M.H. / Chen, Y. / Wang, J.Y. / Yasui, S. / TenDyke, K. / Wu, J. / Ingersoll, C. / Loiacono, K.A. / Hutz, J.E. / Sarwar, N.
History
DepositionJun 15, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 17, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 16, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Mar 6, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id
Revision 1.3Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Stimulator of interferon genes protein
B: Stimulator of interferon genes protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,2819
Polymers43,1622
Non-polymers1,1197
Water68538
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4210 Å2
ΔGint-4 kcal/mol
Surface area16880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)33.733, 77.831, 131.689
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: SER / Beg label comp-ID: SER / End auth comp-ID: GLU / End label comp-ID: GLU / Refine code: _ / Auth seq-ID: 154 - 337 / Label seq-ID: 2 - 185

Dom-IDAuth asym-IDLabel asym-ID
1AA
2BB

-
Components

#1: Protein Stimulator of interferon genes protein / hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / ...hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / Transmembrane protein 173


Mass: 21581.209 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: REF variant / Source: (gene. exp.) Homo sapiens (human) / Gene: STING1, ERIS, MITA, TMEM173 / Production host: Escherichia coli (E. coli) / References: UniProt: Q86WV6
#2: Chemical ChemComp-V5V / (1R,3R,15E,28R,29R,30R,31R,34R,36R,39S,41R)-29,41-difluoro-34,39-disulfanyl-2,33,35,38,40,42-hexaoxa-4,6,9,11,13,18,20,22,25,27-decaaza-34,39-diphosphaoctacyclo[28.6.4.1~3,36~.1~28,31~.0~4,8~.0~7,12~.0~19,24~.0~23,27~]dotetraconta-5,7,9,11,15,19,21,23,25-nonaene 34,39-dioxide (non-preferred name)


Mass: 746.600 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H26F2N10O8P2S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 38 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2 Å3/Da / Density % sol: 38.58 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1M HEPES pH 7.5, 0.2M CaCl2, 15% (w/v) PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.9778 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 17, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9778 Å / Relative weight: 1
ReflectionResolution: 2.76→50 Å / Num. obs: 9340 / % possible obs: 100 % / Redundancy: 12.4 % / Rmerge(I) obs: 0.285 / Net I/σ(I): 12
Reflection shellResolution: 2.77→2.87 Å / Num. unique obs: 875 / CC1/2: 0.765

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
HKL-3000data scaling
PHASERphasing
Cootmodel building
HKL-3000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: D_1000249875

Resolution: 2.77→38.95 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.881 / SU B: 18.05 / SU ML: 0.353 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.443 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2711 434 4.6 %RANDOM
Rwork0.2212 ---
obs0.2235 8910 99.25 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 107.3 Å2 / Biso mean: 45.179 Å2 / Biso min: 21.24 Å2
Baniso -1Baniso -2Baniso -3
1--0.39 Å2-0 Å2-0 Å2
2---2.47 Å20 Å2
3---2.86 Å2
Refinement stepCycle: final / Resolution: 2.77→38.95 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2844 0 120 38 3002
Biso mean--42.7 35.2 -
Num. residues----351
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0030.0133025
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172735
X-RAY DIFFRACTIONr_angle_refined_deg1.2591.7044101
X-RAY DIFFRACTIONr_angle_other_deg1.1161.5966338
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3015345
X-RAY DIFFRACTIONr_dihedral_angle_2_deg26.68821.593182
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.67415499
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.2871528
X-RAY DIFFRACTIONr_chiral_restr0.0470.2381
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.023309
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02651
Refine LS restraints NCS

Ens-ID: 1 / Number: 4963 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.13 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 2.77→2.839 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.343 32 -
Rwork0.288 590 -
obs--90.54 %

+
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