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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ftt
TitleCrystal Structure of human cyclic GMP-AMP synthase in complex with 5-bromo-N-[[2-fluoro-5-(1-methylpyrazol-4-yl)phenyl]methyl]-2-hydroxybenzamide
ComponentsCyclic GMP-AMP synthase
KeywordsTRANSFERASE / IMMUNE RESPONSE / NTASE / DNA SENSOR
Function / homology
Function and homology information


2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / paracrine signaling / STING mediated induction of host immune responses / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / regulation of T cell activation / cGAS/STING signaling pathway / pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway ...2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / paracrine signaling / STING mediated induction of host immune responses / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / regulation of T cell activation / cGAS/STING signaling pathway / pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of double-strand break repair via homologous recombination / nucleosome binding / positive regulation of defense response to virus by host / positive regulation of type I interferon production / 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
: / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.235 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
Revision 1.1Feb 18, 2026Group: Refinement description / Structure summary
Category: pdbx_entry_details / pdbx_initial_refinement_model
Item: _pdbx_entry_details.has_protein_modification

-
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)85,7496
Polymers84,8102
Non-polymers9394
Water1086
1
A: Cyclic GMP-AMP synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,8753
Polymers42,4051
Non-polymers4702
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Cyclic GMP-AMP synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,8753
Polymers42,4051
Non-polymers4702
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)218.774, 46.229, 89.751
Angle α, β, γ (deg.)90.000, 110.390, 90.000
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: 42404.906 Da / Num. of mol.: 2 / 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
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-YPU / 5-bromo-N-{[(5P)-2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-2-hydroxybenzamide


Mass: 404.233 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H15BrFN3O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / 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: 2.51 Å3/Da / Density % sol: 50.96 %
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: 1.00003 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Nov 17, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00003 Å / Relative weight: 1
ReflectionResolution: 2.24→84.13 Å / Num. obs: 41201 / % possible obs: 99.6 % / Redundancy: 3.713 % / Biso Wilson estimate: 67.842 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.109 / Rrim(I) all: 0.128 / Χ2: 0.807 / Net I/σ(I): 6.95 / Num. measured all: 152973 / Scaling rejects: 54
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
2.24-2.293.733.8920.3211137301529864.54399
2.29-2.363.5324.1310.2910352294029314.87199.70.158
2.36-2.423.7312.8170.4710742288528793.28599.80.169
2.42-2.53.8931.9410.7210734276227572.24699.80.348
2.5-2.583.8721.5240.9210645275827491.76799.70.484
2.58-2.673.8081.0841.299821258725791.2699.70.609
2.67-2.773.7280.8331.639361251225110.9721000.708
2.77-2.893.5070.5882.158681248424750.69599.60.803
2.89-3.013.7740.3863.418767233323230.45199.60.892
3.01-3.163.8640.2734.838628223522330.31799.90.949
3.16-3.333.8240.1866.878165214521350.21799.50.979
3.33-3.533.7570.1319.317567202520140.15399.50.987
3.53-3.783.4850.09312.26632191119030.1199.60.991
3.78-4.083.7630.07515.796635177117630.08799.50.994
4.08-4.473.8050.05520.396289165816530.06499.70.997
4.47-53.6580.04822.385388149714730.05698.40.997
5-5.773.3540.04620.894387131413080.05499.50.997
5.77-7.073.7410.04622.684197112611220.05499.60.997
7.07-103.5210.03128.631419008920.03699.10.999
10-56.1493.3090.02534.217045205150.03991

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHENIX1.14_3260refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: inhouse model

Resolution: 2.235→56.149 Å / SU ML: 0.34 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 39.03 / Stereochemistry target values: ML
Details: similar to another structure with this ligand but different space group. The two molecules in the asymmetric unit have the same orientation as cGAS in the DNA complex. Ligand density clear.
RfactorNum. reflection% reflectionSelection details
Rfree0.287 1231 4.7 %RANDOM
Rwork0.2088 24943 --
obs0.2125 26174 63.35 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 179.7 Å2 / Biso mean: 57.1784 Å2 / Biso min: 11.23 Å2
Refinement stepCycle: final / Resolution: 2.235→56.149 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5703 0 52 6 5761
Biso mean--42.26 34.13 -
Num. residues----691
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 9

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.2352-2.32470.712820.363683852
2.3247-2.43050.435960.38863843909
2.4305-2.55860.4767420.35951011105323
2.5586-2.71890.43081080.33322074218248
2.7189-2.92880.37952170.31423737395487
2.9288-3.22350.36562130.285943604573100
3.2235-3.68990.29122190.219943564575100
3.6899-4.64850.24142230.160344164639100
4.6485-56.16660.24232010.16974522472399
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)
14.90594.8587-0.53235.5392-0.17321.3744-0.33690.258-1.15610.0820.212-0.12890.4134-0.26160.0970.57470.12540.1020.24340.00850.493742.075-39.643925.507
21.77712.0925-0.32383.0592-1.41782.18460.10090.2351-0.1513-0.05140.01180.57260.0483-0.2686-0.09360.25890.1114-0.03360.4787-0.1850.594316.1284-22.138120.1312
31.447-1.17970.27671.84690.2293.0283-0.1976-0.3183-0.25710.8820.12370.60190.2058-0.23920.00080.38080.04990.12580.46-0.08530.47614.1728-28.608830.7449
42.0270.14090.47211.6321-0.12.476-0.0101-0.0804-0.08950.0521-0.11160.17-0.1421-0.08010.11820.16270.02370.02270.091-0.04630.097839.2375-19.550120.3352
52.05971.1384-0.28750.7298-0.31050.21620.0924-0.240.3906-0.2293-0.25910.6965-0.2277-0.51810.17270.5397-0.0739-0.05140.6054-0.22930.710925.0842-18.8882-22.3313
62.8285-0.625-0.27860.14130.06410.02440.0835-0.16190.1147-0.3867-0.12121.12720.2355-0.2907-0.01180.4738-0.2416-0.14980.783-0.24810.977914.4715-36.8572-21.792
71.63190.33380.23882.8255-0.28711.93030.05530.19490.118-0.2798-0.03080.7540.0792-0.60030.04460.2905-0.08020.02480.429-0.24610.381725.7954-32.0395-17.8588
82.19620.0459-0.16292.13430.09773.31240.14320.2080.1311-0.1042-0.27170.0969-0.0157-0.1630.11470.11280.0076-0.02360.1746-0.00330.10443.9326-33.8144-24.8745
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 162 through 181 )A162 - 181
2X-RAY DIFFRACTION2chain 'A' and (resid 182 through 272 )A182 - 272
3X-RAY DIFFRACTION3chain 'A' and (resid 273 through 326 )A273 - 326
4X-RAY DIFFRACTION4chain 'A' and (resid 327 through 520 )A327 - 520
5X-RAY DIFFRACTION5chain 'B' and (resid 161 through 218 )B161 - 218
6X-RAY DIFFRACTION6chain 'B' and (resid 219 through 289 )B219 - 289
7X-RAY DIFFRACTION7chain 'B' and (resid 290 through 397 )B290 - 397
8X-RAY DIFFRACTION8chain 'B' and (resid 398 through 520 )B398 - 520

+
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