[English] 日本語
Yorodumi
- PDB-5xze: Mouse cGAS bound to the inhibitor RU332 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5xze
TitleMouse cGAS bound to the inhibitor RU332
Components
  • Cyclic GMP-AMP synthase
  • DNA (5'-D(*AP*AP*AP*TP*TP*GP*CP*CP*GP*AP*AP*GP*AP*CP*G)-3')
  • DNA (5'-D(P*CP*GP*TP*CP*TP*TP*CP*GP*GP*CP*AP*AP*TP*T)-3')
KeywordsIMMUNE SYSTEM/INHIBITOR / Inhibitor / cGAS / STING / IMMUNE SYSTEM-INHIBITOR complex
Function / homology
Function and homology information


regulation of type I interferon production / cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / negative regulation of DNA repair / cGAS/STING signaling pathway / regulation of immunoglobulin production / regulation of T cell activation / pattern recognition receptor signaling pathway ...regulation of type I interferon production / cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / negative regulation of DNA repair / cGAS/STING signaling pathway / regulation of immunoglobulin production / regulation of T cell activation / pattern recognition receptor signaling pathway / negative regulation of double-strand break repair via homologous recombination / negative regulation of cGAS/STING signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / cGMP-mediated signaling / cAMP-mediated signaling / nucleosome binding / positive regulation of type I interferon production / regulation of immune response / positive regulation of defense response to virus by host / phosphatidylinositol-4,5-bisphosphate binding / activation of innate immune response / molecular condensate scaffold activity / determination of adult lifespan / positive regulation of cellular senescence / site of double-strand break / double-stranded DNA binding / defense response to virus / nuclear body / DNA repair / innate immune response / DNA damage response / chromatin binding / GTP binding / protein homodimerization activity / DNA binding / nucleoplasm / ATP binding / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Beta Polymerase; domain 2 - #90 / Poly(a)-polymerase, middle domain - #40 / Poly(a)-polymerase, middle domain / Mab-21-like, nucleotidyltransferase domain / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21 / Beta Polymerase; domain 2 ...Beta Polymerase; domain 2 - #90 / Poly(a)-polymerase, middle domain - #40 / Poly(a)-polymerase, middle domain / Mab-21-like, nucleotidyltransferase domain / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21 / Beta Polymerase; domain 2 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-AE7 / DNA / DNA (> 10) / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.177 Å
AuthorsVincent, J. / Adura, C. / Gao, P. / Luz, A. / Lama, L. / Asano, Y. / Okamoto, R. / Imaeda, T. / Aida, J. / Rothamel, K. ...Vincent, J. / Adura, C. / Gao, P. / Luz, A. / Lama, L. / Asano, Y. / Okamoto, R. / Imaeda, T. / Aida, J. / Rothamel, K. / Gogakos, T. / Steinberg, J. / Reasoner, S. / Aso, K. / Tuschl, T. / Patel, D.J. / Glickman, J.F. / Ascano, M.
CitationJournal: Nat Commun / Year: 2017
Title: Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice.
Authors: Vincent, J. / Adura, C. / Gao, P. / Luz, A. / Lama, L. / Asano, Y. / Okamoto, R. / Imaeda, T. / Aida, J. / Rothamel, K. / Gogakos, T. / Steinberg, J. / Reasoner, S. / Aso, K. / Tuschl, T. / ...Authors: Vincent, J. / Adura, C. / Gao, P. / Luz, A. / Lama, L. / Asano, Y. / Okamoto, R. / Imaeda, T. / Aida, J. / Rothamel, K. / Gogakos, T. / Steinberg, J. / Reasoner, S. / Aso, K. / Tuschl, T. / Patel, D.J. / Glickman, J.F. / Ascano, M.
History
DepositionJul 12, 2017Deposition site: PDBJ / Processing site: RCSB
Revision 1.0Oct 11, 2017Provider: repository / Type: Initial release
Revision 1.1Mar 13, 2024Group: Advisory / Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_residues
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclic GMP-AMP synthase
E: DNA (5'-D(*AP*AP*AP*TP*TP*GP*CP*CP*GP*AP*AP*GP*AP*CP*G)-3')
F: DNA (5'-D(P*CP*GP*TP*CP*TP*TP*CP*GP*GP*CP*AP*AP*TP*T)-3')
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,8175
Polymers51,3863
Non-polymers4312
Water1,47782
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2710 Å2
ΔGint-18 kcal/mol
Surface area22100 Å2
MethodPISA
Unit cell
Length a, b, c (Å)85.285, 98.633, 129.175
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number23
Space group name H-MI222
Components on special symmetry positions
IDModelComponents
11A-728-

HOH

21A-751-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Cyclic GMP-AMP synthase / / m-cGAS / 2'3'-cGAMP synthase / Mab-21 domain-containing protein 1


Mass: 42512.121 Da / Num. of mol.: 1 / Fragment: UNP residues 147-505
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Mb21d1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q8C6L5, cyclic GMP-AMP synthase

-
DNA chain , 2 types, 2 molecules EF

#2: DNA chain DNA (5'-D(*AP*AP*AP*TP*TP*GP*CP*CP*GP*AP*AP*GP*AP*CP*G)-3')


Mass: 4627.037 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Mus musculus (house mouse)
#3: DNA chain DNA (5'-D(P*CP*GP*TP*CP*TP*TP*CP*GP*GP*CP*AP*AP*TP*T)-3')


Mass: 4246.764 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Mus musculus (house mouse)

-
Non-polymers , 3 types, 84 molecules

#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#5: Chemical ChemComp-AE7 / (3R)-3-[1-(3H-1lambda~4~,3-benzothiazol-2-yl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl]-2-benzofuran-1(3H)-one


Mass: 365.406 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H15N3O3S
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 82 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 53.96 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.1 M MES, pH 6.3, 25% PEG400, 0.1 M magnesium chloride

-
Data collection

DiffractionMean temperature: 77 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.979 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 27, 2015
RadiationMonochromator: Cryogenically-cooled single crystal Si(220) side bounce
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.177→50 Å / Num. obs: 28373 / % possible obs: 98.09 % / Redundancy: 3.6 % / Net I/σ(I): 12.8
Reflection shellHighest resolution: 2.177 Å

-
Processing

Software
NameVersionClassification
PHENIX1.8.4_1496refinement
PDB_EXTRACT3.22data extraction
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.177→39.197 Å / SU ML: 0.36 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 35.91
RfactorNum. reflection% reflection
Rfree0.2807 1428 5.03 %
Rwork0.2422 --
obs0.2442 28373 98.09 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 184.38 Å2 / Biso mean: 67.45 Å2 / Biso min: 29.62 Å2
Refinement stepCycle: final / Resolution: 2.177→39.197 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2937 592 26 82 3637
Biso mean--86.72 53.97 -
Num. residues----386
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0093694
X-RAY DIFFRACTIONf_angle_d1.2535095
X-RAY DIFFRACTIONf_chiral_restr0.048549
X-RAY DIFFRACTIONf_plane_restr0.005545
X-RAY DIFFRACTIONf_dihedral_angle_d20.461466
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 10

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.1767-2.25440.40871400.38992496263693
2.2544-2.34470.39871330.3512692282599
2.3447-2.45140.38631480.33382692284099
2.4514-2.58060.34561430.309727092852100
2.5806-2.74230.32951500.301527092859100
2.7423-2.95390.34351280.298127402868100
2.9539-3.25110.30971440.27582718286299
3.2511-3.72120.27491400.2362743288399
3.7212-4.68710.22361580.19632716287498
4.6871-39.20290.24471440.19092730287494
Refinement TLS params.

Method: refined / 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)
13.2589-0.1160.4713.0136-0.24342.43250.05290.46850.4596-0.4954-0.0144-0.0547-0.21430.0962-0.01560.3921-0.07960.04070.40.1070.5271101.3108211.8781293.1301
21.61380.5403-0.22353.3866-1.09072.0160.04230.3489-0.0231-0.5182-0.1668-0.4167-0.09840.39480.09810.4274-0.00650.07190.44630.01620.5192106.7151204.052289.2943
32.5287-0.11060.19542.37871.34632.13690.1066-0.37020.2270.10240.1154-0.6987-0.08510.5166-0.18480.3024-0.06-0.01650.42820.02430.5869107.6158206.1474313.6681
47.55093.81420.35296.7807-2.76998.94580.16651.4387-0.2928-0.67280.254-0.7273-0.1667-0.3189-0.4151.4161-0.14020.17741.75960.00730.965483.8626213.9607279.4493
56.93081.1259-0.84127.93681.32443.75190.203-0.16541.16560.45430.09990.452-0.8536-0.2994-0.19660.53670.02110.10630.30720.02350.619483.6077218.8008304.6611
65.11660.40390.30695.52930.98855.91110.1525-0.12370.2043-0.0670.16480.33180.0864-1.5974-0.32120.56180.0119-0.04110.70240.10510.647882.1032215.6923298.0468
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 149 through 234 )A149 - 234
2X-RAY DIFFRACTION2chain 'A' and (resid 235 through 376 )A235 - 376
3X-RAY DIFFRACTION3chain 'A' and (resid 377 through 505 )A377 - 505
4X-RAY DIFFRACTION4chain 'E' and (resid 1 through 5 )E1 - 5
5X-RAY DIFFRACTION5chain 'E' and (resid 6 through 15 )E6 - 15
6X-RAY DIFFRACTION6chain 'F' and (resid 4 through 17 )F4 - 17

+
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://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