[English] 日本語
Yorodumi
- PDB-8vl7: Co-crystal structure of human TREX1 in complex with an inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vl7
TitleCo-crystal structure of human TREX1 in complex with an inhibitor
ComponentsThree-prime repair exonuclease 1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Trex1 / inhibitor / nuclease / SGC / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


Regulation by TREX1 / immune response in brain or nervous system / adenyl deoxyribonucleotide binding / CD86 biosynthetic process / immune complex formation / atrial cardiac muscle tissue development / activation of immune response / DNA synthesis involved in UV-damage excision repair / T cell antigen processing and presentation / MutSalpha complex binding ...Regulation by TREX1 / immune response in brain or nervous system / adenyl deoxyribonucleotide binding / CD86 biosynthetic process / immune complex formation / atrial cardiac muscle tissue development / activation of immune response / DNA synthesis involved in UV-damage excision repair / T cell antigen processing and presentation / MutSalpha complex binding / retrotransposition / oligosaccharyltransferase complex / regulation of lysosome organization / regulation of fatty acid metabolic process / regulation of lipid biosynthetic process / DNA modification / WW domain binding / heart process / MutLalpha complex binding / regulation of protein complex stability / cellular response to hydroxyurea / lymphoid progenitor cell differentiation / regulation of type I interferon production / double-stranded DNA 3'-5' DNA exonuclease activity / exodeoxyribonuclease III / macrophage activation involved in immune response / regulation of tumor necrosis factor production / IRF3-mediated induction of type I IFN / regulation of cellular respiration / inflammatory response to antigenic stimulus / DNA catabolic process / regulation of immunoglobulin production / apoptotic cell clearance / regulation of T cell activation / regulation of glycolytic process / DNA duplex unwinding / DNA binding, bending / 3'-5'-DNA exonuclease activity / negative regulation of type I interferon-mediated signaling pathway / DNA metabolic process / negative regulation of cGAS/STING signaling pathway / type I interferon-mediated signaling pathway / blood vessel development / nuclear replication fork / cellular response to interferon-beta / mismatch repair / heart morphogenesis / mitotic G1 DNA damage checkpoint signaling / negative regulation of innate immune response / 3'-5' exonuclease activity / generation of precursor metabolites and energy / kidney development / determination of adult lifespan / protein-DNA complex / establishment of protein localization / cellular response to gamma radiation / cellular response to reactive oxygen species / nuclear envelope / single-stranded DNA binding / regulation of inflammatory response / double-stranded DNA binding / DNA recombination / defense response to virus / DNA replication / protein stabilization / DNA repair / endoplasmic reticulum membrane / magnesium ion binding / protein homodimerization activity / metal ion binding / cytoplasm / cytosol
Similarity search - Function
Three-prime repair exonuclease 1/2 / Exonuclease, RNase T/DNA polymerase III / EXOIII / Ribonuclease H superfamily / Ribonuclease H-like superfamily
Similarity search - Domain/homology
Chem-A1ACJ / DI(HYDROXYETHYL)ETHER / Three-prime repair exonuclease 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.88 Å
AuthorsDehghani-Tafti, S. / Dong, A. / Li, Y. / Ackloo, S. / Arrowsmith, C.H. / Edwards, A.M. / Halabelian, L.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: To be published
Title: Co-crystal structure of human TREX1 in complex with an inhibitor
Authors: Dehghani-Tafti, S. / Dong, A. / Li, Y. / Ackloo, S. / Arrowsmith, C.H. / Edwards, A.M. / Halabelian, L.
History
DepositionJan 11, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 24, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Three-prime repair exonuclease 1
B: Three-prime repair exonuclease 1
C: Three-prime repair exonuclease 1
D: Three-prime repair exonuclease 1
E: Three-prime repair exonuclease 1
F: Three-prime repair exonuclease 1
G: Three-prime repair exonuclease 1
H: Three-prime repair exonuclease 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)204,84741
Polymers200,2628
Non-polymers4,58533
Water8,089449
1
A: Three-prime repair exonuclease 1
B: Three-prime repair exonuclease 1
hetero molecules


  • defined by author&software
  • 51.2 kDa, 2 polymers
Theoretical massNumber of molelcules
Total (without water)51,15712
Polymers50,0662
Non-polymers1,09210
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5660 Å2
ΔGint-39 kcal/mol
Surface area19150 Å2
MethodPISA
2
C: Three-prime repair exonuclease 1
D: Three-prime repair exonuclease 1
hetero molecules


  • defined by author&software
  • 51.4 kDa, 2 polymers
Theoretical massNumber of molelcules
Total (without water)51,36610
Polymers50,0662
Non-polymers1,3008
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5340 Å2
ΔGint-39 kcal/mol
Surface area18270 Å2
MethodPISA
3
E: Three-prime repair exonuclease 1
F: Three-prime repair exonuclease 1
hetero molecules


  • defined by author&software
  • 51.3 kDa, 2 polymers
Theoretical massNumber of molelcules
Total (without water)51,25910
Polymers50,0662
Non-polymers1,1948
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5070 Å2
ΔGint-40 kcal/mol
Surface area18710 Å2
MethodPISA
4
G: Three-prime repair exonuclease 1
H: Three-prime repair exonuclease 1
hetero molecules


  • defined by author&software
  • 51.1 kDa, 2 polymers
Theoretical massNumber of molelcules
Total (without water)51,0659
Polymers50,0662
Non-polymers1,0007
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5350 Å2
ΔGint-39 kcal/mol
Surface area18230 Å2
MethodPISA
Unit cell
Length a, b, c (Å)55.827, 56.336, 162.853
Angle α, β, γ (deg.)93.12, 98.22, 99.92
Int Tables number1
Space group name H-MP1

-
Components

-
Protein , 1 types, 8 molecules ABCDEFGH

#1: Protein
Three-prime repair exonuclease 1 / 3'-5' exonuclease TREX1 / Deoxyribonuclease III / DNase III


Mass: 25032.766 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TREX1 / Plasmid: BL21(DE3)V2R-pRARE2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NSU2, exodeoxyribonuclease III

-
Non-polymers , 7 types, 482 molecules

#2: Chemical
ChemComp-A1ACJ / (2P)-2-[3-bromo-2-(2-hydroxyethoxy)phenyl]-5-hydroxy-1-methyl-N-(1,2-oxazol-4-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide


Mass: 451.228 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C17H15BrN4O6 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: Mg
#5: Chemical
ChemComp-UNX / UNKNOWN ATOM OR ION


Num. of mol.: 5 / Source method: obtained synthetically
#6: Chemical ChemComp-PG4 / TETRAETHYLENE GLYCOL


Mass: 194.226 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H18O5 / Comment: precipitant*YM
#7: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 449 / 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: 2.49 Å3/Da / Density % sol: 50.51 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 300mM MgNO4, 26% PEG 3350, 100mM Tris pH 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Aug 1, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 1.88→35 Å / Num. obs: 141898 / % possible obs: 90.6 % / Redundancy: 2 % / CC1/2: 0.994 / CC star: 0.999 / Rmerge(I) obs: 0.063 / Rpim(I) all: 0.058 / Rrim(I) all: 0.086 / Χ2: 1.453 / Net I/σ(I): 14.5 / Num. measured all: 285236
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2CC starRpim(I) allRrim(I) allΧ2% possible all
1.88-1.9120.59470830.6420.8840.560.8181.31690.7
1.91-1.9520.51472880.7030.9090.4820.7061.29392.4
1.95-1.982.10.42671100.7920.940.3990.5851.32992.2
1.98-2.032.10.3672330.8620.9620.3370.4941.37892.5
2.03-2.072.10.29873120.8720.9650.2790.411.492.3
2.07-2.122.10.24471970.9150.9780.2290.3361.41992.4
2.12-2.172.10.272060.9390.9840.1880.2751.39791.8
2.17-2.232.10.17771810.9460.9860.1660.2431.46391.5
2.23-2.2920.14671060.960.990.1370.21.46791
2.29-2.3720.12371020.9720.9930.1140.1681.45691.1
2.37-2.4520.10770880.9760.9940.0990.1461.49389.8
2.45-2.551.90.08969030.9830.9960.0830.1221.57788.3
2.55-2.671.90.07465270.9870.9970.0690.1021.58283.2
2.67-2.8120.0773150.9880.9970.0640.0951.55493.6
2.81-2.9820.05973930.990.9970.0540.081.51794.3
2.98-3.2120.05472150.9870.9970.050.0741.63492.7
3.21-3.5420.04972690.9890.9970.0450.0671.63392.4
3.54-4.051.90.04568820.9880.9970.0410.0621.48287.9
4.05-5.11.80.04362580.990.9970.0390.0581.45479.6
5.1-352.10.03672300.9950.9990.0310.0471.28692.7

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
HKL-3000data scaling
HKL-3000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.88→34.64 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.944 / SU B: 4.189 / SU ML: 0.117 / Cross valid method: THROUGHOUT / ESU R: 0.16 / ESU R Free: 0.148 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23279 7249 5.1 %RANDOM
Rwork0.19228 ---
obs0.19437 134566 90.18 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 36.382 Å2
Baniso -1Baniso -2Baniso -3
1-3.15 Å2-0.61 Å22.23 Å2
2---1.57 Å20.3 Å2
3----1.93 Å2
Refinement stepCycle: 1 / Resolution: 1.88→34.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13130 0 284 449 13863
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.01313896
X-RAY DIFFRACTIONr_bond_other_d0.0010.01712711
X-RAY DIFFRACTIONr_angle_refined_deg1.2831.64518885
X-RAY DIFFRACTIONr_angle_other_deg1.2121.57329467
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.06251751
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.08621.16569
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.326151962
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.1251583
X-RAY DIFFRACTIONr_chiral_restr0.060.21790
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0216223
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022750
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.5453.827064
X-RAY DIFFRACTIONr_mcbond_other2.5453.827065
X-RAY DIFFRACTIONr_mcangle_it3.685.7078791
X-RAY DIFFRACTIONr_mcangle_other3.685.7078791
X-RAY DIFFRACTIONr_scbond_it2.8384.0686832
X-RAY DIFFRACTIONr_scbond_other2.8374.0686833
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other4.3496.04310095
X-RAY DIFFRACTIONr_long_range_B_refined6.07745.96414683
X-RAY DIFFRACTIONr_long_range_B_other6.07645.96514684
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.88→1.927 Å
RfactorNum. reflection% reflection
Rfree0.358 545 -
Rwork0.324 9519 -
obs--86.68 %

+
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://pdbjlvh1.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