[English] 日本語
Yorodumi
- PDB-7ftu: Crystal Structure of human cyclic GMP-AMP synthase in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ftu
TitleCrystal Structure of human cyclic GMP-AMP synthase in complex with (Z)-N-[4-(4-chlorophenyl)sulfonylphenyl]-2-cyano-3-hydroxy-3-(5-methyl-1,2-oxazol-4-yl)prop-2-enamide
ComponentsCyclic GMP-AMP synthase
KeywordsTRANSFERASE / NUCLEOTIDYLTRANSFERASE / CYCLIC GMP-AMP SYNTHASE / CGAS / DNA-BINDING / ACTIVATOR DNA / PATTERN RECOGNITION RECEPTOR / INNATE IMMUNE RESPONSE / VIRAL DNA RECOGNITION
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 / : ...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 / : / 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 / : / 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 / cytoplasm / cytosol
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
ADENOSINE-5'-TRIPHOSPHATE / : / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.65 Å
AuthorsLeibrock, L. / Benz, J. / Groebke-Zbinden, K. / Rudolph, M.G.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
F. Hoffmann-La Roche LTD Switzerland
CitationJournal: To be published
Title: Crystal Structure of a human cyclic GMP-AMP synthase complex
Authors: Groebke-Zbinden, K. / Vandemeulebroucke, A. / Hilbert, M. / Rudolph, M.G.
History
DepositionFeb 8, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 21, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclic GMP-AMP synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,5667
Polymers42,4051
Non-polymers1,1616
Water3,225179
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, elutes as a monomer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)50.027, 60.216, 126.432
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21221

-
Components

-
Protein , 1 types, 1 molecules A

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


Mass: 42404.906 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 161-522
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CGAS, C6orf150, MB21D1 / Plasmid: pET21a_cGAS(161-522_wt) / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q8N884, cyclic GMP-AMP synthase

-
Non-polymers , 6 types, 185 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Chemical ChemComp-YPD / (2Z)-N-[4-(4-chlorobenzene-1-sulfonyl)phenyl]-2-cyano-3-hydroxy-3-(5-methyl-1,2-oxazol-4-yl)prop-2-enamide


Mass: 443.860 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H14ClN3O5S
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 179 / 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: 2.25 Å3/Da / Density % sol: 45.22 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 10-12 mg/mL protein in 25 mM Tris/HCl pH7.5, 500mM NaCl, 2mM TCEP, supplemented with 10x molar excess of ligand and, if needed, with 10 mM MgCl2 and 5mM ATP, then mixed 1:1 with reservoir of ...Details: 10-12 mg/mL protein in 25 mM Tris/HCl pH7.5, 500mM NaCl, 2mM TCEP, supplemented with 10x molar excess of ligand and, if needed, with 10 mM MgCl2 and 5mM ATP, then mixed 1:1 with reservoir of the Procomplex screen. Several conditions resulted in crystals

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00002 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Dec 13, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00002 Å / Relative weight: 1
ReflectionResolution: 1.65→63.22 Å / Num. obs: 45593 / % possible obs: 97.3 % / Redundancy: 6.166 % / Biso Wilson estimate: 42.812 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.056 / Rrim(I) all: 0.061 / Χ2: 0.859 / Net I/σ(I): 13.24 / Num. measured all: 281108 / Scaling rejects: 3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsRrim(I) all% possible allCC1/2
1.65-1.694.123.7960.3211107340626964.34479.2
1.69-1.744.6272.7460.513603333129403.09288.30.208
1.74-1.795.4771.8930.8317247324331492.09197.10.491
1.79-1.846.7241.3711.3420852311231011.48799.60.676
1.84-1.916.7521.0451.7820653306430591.13499.80.769
1.91-1.976.6570.7692.4819758297529680.83599.80.86
1.97-2.056.3410.5433.5117997284728380.59299.70.935
2.05-2.136.6360.3695.1718302276727580.40199.70.966
2.13-2.226.8330.2687.2918005264326350.2999.70.984
2.22-2.336.6730.1919.7916877253525290.20799.80.989
2.33-2.466.3950.13912.615457241924170.15199.90.993
2.46-2.616.5110.10316.3115067231523140.1131000.997
2.61-2.796.6780.07921.0514318214821440.08699.80.997
2.79-3.016.5510.0592713194201620140.06499.90.998
3.01-3.36.0030.04532.4311232187218710.04999.90.999
3.3-3.696.4740.03441.8710954169216920.0371000.999
3.69-4.266.1770.0346.229401152615220.03399.70.999
4.26-5.225.8110.02948.547496129512900.03299.60.999
5.22-7.386.0790.02848.796286103610340.0399.80.999
7.38-63.225.3090.02349.6533026246220.02699.70.999

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
REFMAC5.8.0403refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: inhouse model

Resolution: 1.65→63.22 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.935 / SU B: 6.218 / SU ML: 0.104 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.159 / ESU R Free: 0.148 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: ligand occupies position of guanosine nucleotide. ATP binding mode and protein; conformation are very similar to mouse cGAS structure 4k97 that has ATP and DNA bound.; ligand density very ...Details: ligand occupies position of guanosine nucleotide. ATP binding mode and protein; conformation are very similar to mouse cGAS structure 4k97 that has ATP and DNA bound.; ligand density very clear. Similar to 2gas5.;
RfactorNum. reflection% reflectionSelection details
Rfree0.2471 1663 5 %RANDOM
Rwork0.2058 ---
obs0.2077 31541 70.28 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 97.47 Å2 / Biso mean: 33.145 Å2 / Biso min: 15.18 Å2
Baniso -1Baniso -2Baniso -3
1-0.2 Å20 Å2-0 Å2
2---0.17 Å20 Å2
3----0.03 Å2
Refinement stepCycle: final / Resolution: 1.65→63.22 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2923 0 69 179 3171
Biso mean--30.93 34.85 -
Num. residues----355
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0123068
X-RAY DIFFRACTIONr_bond_other_d0.0010.0162930
X-RAY DIFFRACTIONr_angle_refined_deg1.1311.6494111
X-RAY DIFFRACTIONr_angle_other_deg0.3791.5876774
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7735354
X-RAY DIFFRACTIONr_dihedral_angle_2_deg4.395520
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.53210597
X-RAY DIFFRACTIONr_chiral_restr0.0540.2441
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.023455
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02709
X-RAY DIFFRACTIONr_mcbond_it1.3092.3491419
X-RAY DIFFRACTIONr_mcbond_other1.3092.3491419
X-RAY DIFFRACTIONr_mcangle_it2.1384.2061769
LS refinement shellResolution: 1.645→1.688 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.831 8 -
Rwork0.444 102 -
all-110 -
obs--3.19 %
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)
11.22020.35990.07721.18310.04221.1852-0.0406-0.0911-0.2942-0.1068-0.011-0.02380.30340.17750.05150.08990.04930.02220.03540.03370.078713.72715.486614.0158
21.0854-0.24590.30220.9433-0.26681.4303-0.0286-0.146-0.2077-0.1143-0.02410.04840.36430.06090.05270.11250.02960.02440.03780.05070.077111.45916.252517.5941
31.13190.25530.8110.47020.23241.8681-0.1075-0.16220.0665-0.0445-0.00330.0636-0.08140.030.11090.0180.0185-0.0220.0574-0.00290.041213.66227.683320.6104
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A162 - 272
2X-RAY DIFFRACTION2A273 - 387
3X-RAY DIFFRACTION3A388 - 521

+
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