[English] 日本語
Yorodumi
- PDB-7kp9: asymmetric hTNF-alpha -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7kp9
Titleasymmetric hTNF-alpha
ComponentsTumor necrosis factor
KeywordsCYTOKINE / Tumour necrosis factor alpha / TNF / asymmetric / protein-protein inhibitor
Function / homology
Function and homology information


negative regulation of L-glutamate import across plasma membrane / negative regulation of branching involved in lung morphogenesis / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of interleukin-33 production / positive regulation of neutrophil activation / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / positive regulation of leukocyte adhesion to arterial endothelial cell ...negative regulation of L-glutamate import across plasma membrane / negative regulation of branching involved in lung morphogenesis / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of interleukin-33 production / positive regulation of neutrophil activation / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / positive regulation of leukocyte adhesion to arterial endothelial cell / positive regulation of vitamin D biosynthetic process / positive regulation of translational initiation by iron / response to macrophage colony-stimulating factor / regulation of membrane lipid metabolic process / regulation of endothelial cell apoptotic process / chronic inflammatory response to antigenic stimulus / regulation of branching involved in salivary gland morphogenesis / positive regulation of I-kappaB phosphorylation / negative regulation of protein-containing complex disassembly / response to 3,3',5-triiodo-L-thyronine / response to gold nanoparticle / positive regulation of humoral immune response mediated by circulating immunoglobulin / positive regulation of hair follicle development / negative regulation of myelination / negative regulation of bicellular tight junction assembly / negative regulation of cytokine production involved in immune response / negative regulation of vascular wound healing / : / negative regulation of amyloid-beta clearance / response to isolation stress / triglyceride storage / positive regulation of interleukin-18 production / positive regulation of action potential / inflammatory response to wounding / death receptor agonist activity / positive regulation of protein transport / TNF signaling / epithelial cell proliferation involved in salivary gland morphogenesis / toll-like receptor 3 signaling pathway / embryonic digestive tract development / vascular endothelial growth factor production / necroptotic signaling pathway / leukocyte migration involved in inflammatory response / response to fructose / positive regulation of neuroinflammatory response / positive regulation of synoviocyte proliferation / positive regulation of calcineurin-NFAT signaling cascade / leukocyte tethering or rolling / cellular response to toxic substance / positive regulation of mononuclear cell migration / positive regulation of fever generation / negative regulation of myoblast differentiation / endothelial cell apoptotic process / regulation of establishment of endothelial barrier / negative regulation of D-glucose import / negative regulation of oxidative phosphorylation / macrophage activation involved in immune response / positive regulation of protein localization to cell surface / positive regulation of osteoclast differentiation / positive regulation of protein-containing complex disassembly / tumor necrosis factor receptor binding / positive regulation of cytokine production involved in inflammatory response / TNFR1-mediated ceramide production / negative regulation of systemic arterial blood pressure / positive regulation of heterotypic cell-cell adhesion / regulation of immunoglobulin production / positive regulation of hepatocyte proliferation / positive regulation of programmed cell death / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of podosome assembly / positive regulation of membrane protein ectodomain proteolysis / positive regulation of extrinsic apoptotic signaling pathway / regulation of metabolic process / regulation of canonical NF-kappaB signal transduction / regulation of fat cell differentiation / positive regulation of leukocyte adhesion to vascular endothelial cell / TNFR1-induced proapoptotic signaling / regulation of reactive oxygen species metabolic process / negative regulation of heart rate / positive regulation of amyloid-beta formation / positive regulation of DNA biosynthetic process / response to L-glutamate / negative regulation of viral genome replication / regulation of synapse organization / negative regulation of fat cell differentiation / negative regulation of endothelial cell proliferation / Interleukin-10 signaling / negative regulation of interleukin-6 production / negative regulation of blood vessel endothelial cell migration / negative regulation of apoptotic signaling pathway / humoral immune response / negative regulation of mitotic cell cycle / negative regulation of lipid storage / phagocytic cup / extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / skeletal muscle contraction / negative regulation of osteoblast differentiation / cell surface receptor signaling pathway via JAK-STAT / positive regulation of synaptic transmission
Similarity search - Function
Tumour necrosis factor alpha / Tumour necrosis factor / Tumour necrosis factor, conserved site / Tumor necrosis factor (TNF) homology domain (THD) signature. / Tumour necrosis factor family. / TNF(Tumour Necrosis Factor) family / Tumour necrosis factor domain / Tumor necrosis factor (TNF) homology domain (THD) profile. / Tumour necrosis factor-like domain superfamily
Similarity search - Domain/homology
Chem-A7G / Tumor necrosis factor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsArakaki, T.L. / Abendroth, J. / Fairman, J.W. / Foley, A. / Ceska, T.
CitationJournal: Nat Commun / Year: 2021
Title: Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF.
Authors: McMillan, D. / Martinez-Fleites, C. / Porter, J. / Fox 3rd, D. / Davis, R. / Mori, P. / Ceska, T. / Carrington, B. / Lawson, A. / Bourne, T. / O'Connell, J.
History
DepositionNov 10, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 13, 2021Provider: repository / Type: Initial release
Revision 1.1Feb 3, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Apr 3, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tumor necrosis factor
B: Tumor necrosis factor
C: Tumor necrosis factor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,8234
Polymers52,3733
Non-polymers4491
Water3,243180
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5040 Å2
ΔGint-28 kcal/mol
Surface area18030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)54.520, 81.960, 93.240
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Tumor necrosis factor / Cachectin / TNF-alpha / Tumor necrosis factor ligand superfamily member 2 / TNF-a


Mass: 17457.736 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TNF, TNFA, TNFSF2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01375
#2: Chemical ChemComp-A7G / 1-{[2-(difluoromethoxy)phenyl]methyl}-2-methyl-6-[6-(piperazin-1-yl)pyridin-3-yl]-1H-benzimidazole


Mass: 449.496 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H25F2N5O / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 180 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2 Å3/Da / Density % sol: 38.6 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 9
Details: 21.44% PEG 3350, 100 mM Tris pH9.0, vapor diffusion, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.9786 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Nov 30, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9786 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 23367 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Redundancy: 4.9 % / Biso Wilson estimate: 31.831 Å2 / Rmerge(I) obs: 0.092 / Net I/σ(I): 14.19
Reflection shell
Resolution (Å)Rmerge(I) obsMean I/σ(I) obsNum. unique obsDiffraction-ID% possible all
2.15-2.210.5033.117161100
2.21-2.270.4693.71651199.9
2.27-2.330.4044.41607199.8
2.33-2.40.3584.815571100
2.4-2.480.3035.715411100
2.48-2.570.2746.414631100
2.57-2.670.201814191100
2.67-2.780.1689.81375199.9
2.78-2.90.15110.71324199.8
2.9-3.040.1213.112621100
3.04-3.210.08417.11206199.9
3.21-3.40.0720.61152199.9
3.4-3.630.05723.91072199.7
3.63-3.930.0526.210081100
3.93-4.30.04131.59281100
4.3-4.810.03536848199.9
4.81-5.550.03634.37661100
5.55-6.80.03931.5656199.8
6.8-9.620.03434.6514199.8
9.62-500.0337.1302197.4

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
XDSdata reduction
XSCALEdata scaling
REFMAC5.7.0032phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: unpublished structure

Resolution: 2.15→47.06 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.916 / SU B: 5.306 / SU ML: 0.139 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.255 / ESU R Free: 0.206 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.241 1149 4.9 %RANDOM
Rwork0.188 22218 --
obs0.19 23367 99.81 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 26.379 Å2
Baniso -1Baniso -2Baniso -3
1-0.82 Å20 Å2-0 Å2
2---0.89 Å2-0 Å2
3---0.07 Å2
Refinement stepCycle: LAST / Resolution: 2.15→47.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3134 0 33 180 3347
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0193269
X-RAY DIFFRACTIONr_bond_other_d0.0010.023079
X-RAY DIFFRACTIONr_angle_refined_deg1.4861.9754475
X-RAY DIFFRACTIONr_angle_other_deg0.7352.9947026
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.6115417
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.63124.462130
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.22115476
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.7021514
X-RAY DIFFRACTIONr_chiral_restr0.0890.2518
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0213724
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02722
X-RAY DIFFRACTIONr_mcbond_it2.2942.7091671
X-RAY DIFFRACTIONr_mcbond_other2.2932.7081672
X-RAY DIFFRACTIONr_mcangle_it3.6494.0222073
LS refinement shellResolution: 2.15→2.206 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.321 73 -
Rwork0.233 1635 -
all-1708 -
obs--99.82 %

+
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