[English] 日本語
Yorodumi
- PDB-9j2w: Human cGAS catalytic domain bound with XL-3156 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9j2w
TitleHuman cGAS catalytic domain bound with XL-3156
ComponentsCyclic GMP-AMP synthase
KeywordsIMMUNE SYSTEM / cGAS / inhibitor
Function / homology
Function and homology information


2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / cGAS/STING signaling pathway / regulation of T cell activation / pattern recognition receptor signaling pathway / cGMP-mediated signaling ...2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / cGAS/STING signaling pathway / regulation of T cell activation / pattern recognition receptor signaling pathway / cGMP-mediated signaling / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cellular response to exogenous dsRNA / positive regulation of type I interferon production / negative regulation of double-strand break repair via homologous recombination / cAMP-mediated signaling / nucleosome binding / positive regulation of defense response to virus by host / phosphatidylinositol-4,5-bisphosphate binding / activation of innate immune response / determination of adult lifespan / molecular condensate scaffold activity / positive regulation of cellular senescence / site of double-strand break / double-stranded DNA binding / defense response to virus / nuclear body / innate immune response / DNA repair / 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
Mab-21-like, nucleotidyltransferase domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21
Similarity search - Domain/homology
: / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsZhao, W.F. / Li, M.J. / Xu, Y.C.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Discovery of novel cGAS inhibitors
Authors: Zhao, W.F. / Xu, Y.C.
History
DepositionAug 7, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jun 4, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclic GMP-AMP synthase
B: Cyclic GMP-AMP synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)86,6846
Polymers85,5192
Non-polymers1,1664
Water1,26170
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)216.292, 47.502, 87.581
Angle α, β, γ (deg.)90.00, 113.53, 90.00
Int Tables number5
Space group name H-MC121

-
Components

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


Mass: 42759.270 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CGAS, C6orf150, MB21D1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q8N884, cyclic GMP-AMP synthase
#2: Chemical ChemComp-A1EAH / 2-(1~{H}-benzimidazol-2-yl)-4-[[1-(1~{H}-benzimidazol-2-yl)-3-methyl-5-oxidanyl-pyrazol-4-yl]-pyridin-2-yl-methyl]-5-methyl-pyrazol-3-ol


Mass: 517.541 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C28H23N9O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 70 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.41 Å3/Da / Density % sol: 49 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 18-20% V/V PEG 3350, 0.2 M AMMONIUM CITRATE

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.979 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 13, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. obs: 40994 / % possible obs: 97.6 % / Redundancy: 12.6 % / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.106 / Rpim(I) all: 0.03 / Rrim(I) all: 0.11 / Χ2: 0.989 / Net I/σ(I): 6.7 / Num. measured all: 517408
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2CC starRpim(I) allRrim(I) allΧ2% possible all
2.2-2.288.80.88937430.9110.9770.2810.9340.85290.1
2.28-2.3710.40.79940200.9310.9820.2440.8370.89496
2.37-2.4812.80.6841110.9580.9890.1930.7080.9199.2
2.48-2.6113.60.51941210.9680.9920.1440.5390.91199.2
2.61-2.7713.20.36241470.9850.9960.1020.3760.92199.1
2.77-2.9913.40.22340980.9930.9980.0620.2320.93898.2
2.99-3.2913.90.13841610.9960.9990.0380.1431.02299.3
3.29-3.76130.08741310.9980.9990.0250.0911.13198.3
3.76-4.74140.06342090.99810.0170.0661.14198.8
4.74-5012.70.05542530.99910.0160.0571.07897.7

-
Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
HKL-2000data scaling
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4lev

4lev


Resolution: 2.2→32.92 Å / SU ML: 0.24 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.65 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.259 1805 4.83 %
Rwork0.2311 --
obs0.2324 37371 88.59 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.2→32.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5278 0 80 70 5428
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0045462
X-RAY DIFFRACTIONf_angle_d0.8577344
X-RAY DIFFRACTIONf_dihedral_angle_d16.7812072
X-RAY DIFFRACTIONf_chiral_restr0.058808
X-RAY DIFFRACTIONf_plane_restr0.005916
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2-2.260.3711900.29121550X-RAY DIFFRACTION51
2.26-2.320.3125790.29241914X-RAY DIFFRACTION62
2.32-2.40.30871120.27422230X-RAY DIFFRACTION73
2.4-2.480.35061320.26842598X-RAY DIFFRACTION85
2.48-2.580.26911580.26532913X-RAY DIFFRACTION96
2.58-2.70.27621590.25862979X-RAY DIFFRACTION98
2.7-2.840.28971540.2463024X-RAY DIFFRACTION98
2.84-3.020.31061610.24983047X-RAY DIFFRACTION99
3.02-3.250.25151420.24483057X-RAY DIFFRACTION99
3.25-3.580.24261240.22753088X-RAY DIFFRACTION99
3.58-4.10.22511840.23003X-RAY DIFFRACTION98
4.1-5.160.22561420.18753093X-RAY DIFFRACTION98
5.16-32.920.24241680.2333070X-RAY DIFFRACTION96
Refinement TLS params.Method: refined / Origin x: 31.1892 Å / Origin y: 17.7724 Å / Origin z: -0.4669 Å
111213212223313233
T0.1621 Å2-0.0136 Å2-0.0148 Å2-0.2225 Å2-0.0406 Å2--0.2959 Å2
L0.6831 °2-0.2121 °2-0.2582 °2-0.9188 °20.6576 °2--1.859 °2
S0.0065 Å °0.1039 Å °-0.0692 Å °-0.0113 Å °-0.1648 Å °0.3263 Å °-0.0128 Å °-0.4596 Å °0.1255 Å °
Refinement TLS groupSelection details: all

+
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