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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7fur
TitleCrystal Structure of human cyclic GMP-AMP synthase in complex with 1-[9-(6-aminopyridin-3-yl)-6,7-dichloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl]-2-hydroxyethanone
ComponentsCyclic GMP-AMP synthase
KeywordsTRANSFERASE / IMMUNE RESPONSE / NTASE / DNA SENSOR
Function / homology
Function and homology information


cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / 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 ...cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / 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 / 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
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
Similarity search - Domain/homology
ADENOSINE-5'-TRIPHOSPHATE / Chem-JUJ / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 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)43,4176
Polymers42,4051
Non-polymers1,0125
Water3,045169
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)46.886, 58.251, 127.017
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 , 5 types, 174 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 / Adenosine triphosphate


Mass: 507.181 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM
#5: Chemical ChemComp-JUJ / 1-[9-(6-aminopyridin-3-yl)-6,7-dichloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]-2-hydroxyethan-1-one


Mass: 391.251 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H16Cl2N4O2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 169 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.05 Å3/Da / Density % sol: 39.86 %
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: 0.99987 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 6, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99987 Å / Relative weight: 1
ReflectionResolution: 1.7→52.95 Å / Num. obs: 38797 / % possible obs: 99 % / Redundancy: 6.277 % / Biso Wilson estimate: 51.502 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.053 / Rrim(I) all: 0.058 / Χ2: 0.873 / Net I/σ(I): 11.91 / Num. measured all: 243519 / Scaling rejects: 29
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
1.7-1.744.0884.2140.2910531284125764.8290.7
1.74-1.795.0083.1870.4813578277127113.54997.80.218
1.79-1.846.3172.2540.8417056270327002.45499.90.413
1.84-1.96.8551.5321.3418007263326271.65699.80.63
1.9-1.966.9011.0142.0417694257225641.09599.70.809
1.96-2.036.8790.6992.9916833245224470.75699.80.889
2.03-2.116.760.4344.5516034238223720.4799.60.952
2.11-2.196.5570.3156.0815022229422910.34299.90.97
2.19-2.296.2790.2168.2113846221022050.23599.80.982
2.29-2.46.8060.16611.0714469213221260.17999.70.992
2.4-2.536.8780.12314.2913832201220110.1331000.994
2.53-2.696.8110.09517.5813138193119290.10399.90.997
2.69-2.876.6240.07521.6812023181618150.08299.90.997
2.87-3.16.2040.06125.4810441168316830.0671000.997
3.1-3.45.860.05229.559189156815680.0571000.998
3.4-3.86.4450.04634.459132141814170.0599.90.998
3.8-4.396.3530.04136.338062127012690.04499.90.998
4.39-5.386.1440.03836.566734109610960.0411000.998
5.38-7.65.6690.03735.0849048668650.04199.90.998
7.6-52.955.7030.03436.1429945295250.03799.20.999

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHENIX1.17.1_3660refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: inhouse model

Resolution: 1.7→52.95 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 31.58 / Stereochemistry target values: ML
Details: ligand binds to Mg2+ ion in bidentate fashion. binding in presence of ATP explains non-competitiveness in enzymatic assay
RfactorNum. reflection% reflectionSelection details
Rfree0.2379 1428 4.93 %RANDOM
Rwork0.1885 27542 --
obs0.1908 28970 73.94 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 141.64 Å2 / Biso mean: 48.0909 Å2 / Biso min: 20.89 Å2
Refinement stepCycle: final / Resolution: 1.7→52.95 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2964 0 60 169 3193
Biso mean--34.98 43.41 -
Num. residues----360
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 (%)
1.7-1.760.3956170.370636938610
1.76-1.830.3988470.330690395025
1.83-1.910.3214860.28051682176846
1.91-2.010.28241270.25552520264768
2.01-2.140.25111650.23523237340288
2.14-2.310.26792000.22043664386499
2.31-2.540.26911890.212137033892100
2.54-2.910.25772060.208237243930100
2.91-3.660.23162090.185837643973100
3.66-52.950.21221820.160439764158100
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)
11.63410.16580.67576.3105-0.29791.8155-0.1395-0.16220.1481.25090.1573-1.0802-0.15130.39640.13340.38050.0562-0.04660.46940.03980.333125.4536-12.3345-7.2852
22.02570.62070.40613.4513-0.72272.82040.06670.08470.54440.0838-0.10870.0418-0.2853-0.17670.01910.26950.0636-0.01580.3820.03260.34689.9881-2.8871-15.8352
31.4181-0.6327-0.46192.98010.59622.76960.12760.11831.091-0.3293-0.16640.0811-0.7762-0.30490.00090.4439-0.0072-0.07590.27530.15270.641811.465511.0699-19.1297
41.94460.3374-0.30812.7011-0.60331.7607-0.07160.23630.2643-0.1692-0.008-0.0924-0.10850.03220.01350.17560.0306-0.06050.26790.00740.20459.8344-9.8053-14.4858
52.0366-0.447-0.73152.3963-0.91442.9407-0.07330.2232-0.158-0.5136-0.1462-0.17240.42370.19120.16890.29130.01030.00050.2306-0.00630.235914.2126-26.2465-23.1719
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 162 through 199 )A162 - 199
2X-RAY DIFFRACTION2chain 'A' and (resid 200 through 253 )A200 - 253
3X-RAY DIFFRACTION3chain 'A' and (resid 254 through 290 )A254 - 290
4X-RAY DIFFRACTION4chain 'A' and (resid 291 through 405 )A291 - 405
5X-RAY DIFFRACTION5chain 'A' and (resid 406 through 521 )A406 - 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