[English] 日本語
Yorodumi
- PDB-6ooz: Asymmetric hTNF-alpha -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ooz
TitleAsymmetric hTNF-alpha
ComponentsTumor necrosis factor
KeywordsCYTOKINE / Tumour necrosis factor alpha / TNF / asymmetric / protein-protein interaction inhibitor / rheumatoid arthritis
Function / homology
Function and homology information


response to Gram-negative bacterium / negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of fractalkine production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / response to 3,3',5-triiodo-L-thyronine ...response to Gram-negative bacterium / negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of fractalkine production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / response to 3,3',5-triiodo-L-thyronine / : / death receptor agonist activity / positive regulation of protein transport / positive regulation of vitamin D biosynthetic process / positive regulation of translational initiation by iron / regulation of endothelial cell apoptotic process / regulation of branching involved in salivary gland morphogenesis / chronic inflammatory response to antigenic stimulus / response to macrophage colony-stimulating factor / negative regulation of protein-containing complex disassembly / positive regulation of humoral immune response mediated by circulating immunoglobulin / positive regulation of leukocyte adhesion to arterial endothelial cell / response to gold nanoparticle / negative regulation of myelination / positive regulation of JUN kinase activity / negative regulation of vascular wound healing / negative regulation of amyloid-beta clearance / negative regulation of cytokine production involved in immune response / reactive gliosis / positive regulation of hair follicle development / positive regulation of interleukin-18 production / inflammatory response to wounding / response to resveratrol / positive regulation of action potential / epithelial cell proliferation involved in salivary gland morphogenesis / response to quercetin / TNF signaling / toll-like receptor 3 signaling pathway / vascular endothelial growth factor production / negative regulation of D-glucose import across plasma membrane / embryonic digestive tract development / positive regulation of fever generation / positive regulation of calcineurin-NFAT signaling cascade / necroptotic signaling pathway / positive regulation of synoviocyte proliferation / leukocyte tethering or rolling / negative regulation of myoblast differentiation / positive regulation of mononuclear cell migration / response to fructose / positive regulation of hepatocyte proliferation / regulation of establishment of endothelial barrier / endothelial cell apoptotic process / negative regulation of oxidative phosphorylation / response to hydrogen sulfide / positive regulation of protein-containing complex disassembly / positive regulation of protein localization to cell surface / positive regulation of osteoclast differentiation / cellular response to toxic substance / macrophage activation involved in immune response / tumor necrosis factor receptor binding / positive regulation of macrophage derived foam cell differentiation / negative regulation of mitotic cell cycle / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of cytokine production involved in inflammatory response / positive regulation of podosome assembly / regulation of fat cell differentiation / positive regulation of heterotypic cell-cell adhesion / positive regulation of programmed cell death / positive regulation of membrane protein ectodomain proteolysis / regulation of canonical NF-kappaB signal transduction / response to L-glutamate / negative regulation of systemic arterial blood pressure / positive regulation of leukocyte adhesion to vascular endothelial cell / TNFR1-induced proapoptotic signaling / positive regulation of extrinsic apoptotic signaling pathway / TNFR1-mediated ceramide production / mRNA stabilization / regulation of reactive oxygen species metabolic process / negative regulation of heart rate / positive regulation of DNA biosynthetic process / positive regulation of amyloid-beta formation / positive regulation of neuroinflammatory response / negative regulation of viral genome replication / negative regulation of bicellular tight junction assembly / positive regulation of immunoglobulin production / negative regulation of fat cell differentiation / negative regulation of endothelial cell proliferation / response to isolation stress / positive regulation of MAP kinase activity / Interleukin-10 signaling / regulation of synapse organization / regulation of insulin secretion / humoral immune response / negative regulation of interleukin-6 production / histone H3K9ac reader activity / negative regulation of blood vessel endothelial cell migration / negative regulation of apoptotic signaling pathway / negative regulation of lipid storage / extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of glial cell proliferation
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 / Jelly Rolls - #40 / Tumour necrosis factor domain / Tumor necrosis factor (TNF) homology domain (THD) profile. / Tumour necrosis factor-like domain superfamily ...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 / Jelly Rolls - #40 / Tumour necrosis factor domain / Tumor necrosis factor (TNF) homology domain (THD) profile. / Tumour necrosis factor-like domain superfamily / Jelly Rolls / Sandwich / Mainly Beta
Similarity search - Domain/homology
Chem-A6Y / Tumor necrosis factor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsArakaki, T.L. / Edwards, T.E. / Fox III, D. / Lecomte, F. / Ceska, T.
CitationJournal: Nat Commun / Year: 2019
Title: Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer.
Authors: O'Connell, J. / Porter, J. / Kroeplien, B. / Norman, T. / Rapecki, S. / Davis, R. / McMillan, D. / Arakaki, T. / Burgin, A. / Fox Iii, D. / Ceska, T. / Lecomte, F. / Maloney, A. / Vugler, A. ...Authors: O'Connell, J. / Porter, J. / Kroeplien, B. / Norman, T. / Rapecki, S. / Davis, R. / McMillan, D. / Arakaki, T. / Burgin, A. / Fox Iii, D. / Ceska, T. / Lecomte, F. / Maloney, A. / Vugler, A. / Carrington, B. / Cossins, B.P. / Bourne, T. / Lawson, A.
History
DepositionApr 23, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 25, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 1, 2020Group: 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_PubMed / _citation.title / _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 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
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)52,4915
Polymers52,1123
Non-polymers3792
Water79344
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, Runs as trimer by gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5080 Å2
ΔGint-38 kcal/mol
Surface area18300 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.520, 81.170, 93.350
Angle α, β, γ (deg.)90.00, 90.00, 90.00
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: 17370.658 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-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#3: Chemical ChemComp-A6Y / (S)-{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}(pyridin-4-yl)methanol


Mass: 343.422 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H21N3O / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 44 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.95 Å3/Da / Density % sol: 36.9 %
Crystal growTemperature: 289 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 10% PEG 2000, 15% PEG 3350, 3% XYLITOL, 0.1 M HEPES, PH 8.0, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 289K

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 24, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 2.8→20 Å / Num. obs: 10469 / % possible obs: 99.4 % / Observed criterion σ(I): -3 / Redundancy: 4.3 % / Biso Wilson estimate: 38.9 Å2 / Rmerge(I) obs: 0.092 / Net I/σ(I): 15
Reflection shellResolution: 2.8→2.87 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.527 / Mean I/σ(I) obs: 2.9 / Num. unique obs: 1012 / % possible all: 99.7

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
REFMAC5.8.0158refinement
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: unpublished structure

Resolution: 2.8→19.83 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.864 / SU B: 16.861 / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.465 / Details: HYDROGENS HAVE BEEN ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.273 1028 9.9 %RANDOM
Rwork0.183 ---
obs0.192 10432 99.5 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 37.23 Å2
Baniso -1Baniso -2Baniso -3
1-0.69 Å20 Å20 Å2
2---1.66 Å20 Å2
3---0.97 Å2
Refinement stepCycle: LAST / Resolution: 2.8→19.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3162 0 27 44 3233
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0193258
X-RAY DIFFRACTIONr_bond_other_d0.0020.022993
X-RAY DIFFRACTIONr_angle_refined_deg1.5341.9714440
X-RAY DIFFRACTIONr_angle_other_deg0.9732.9936900
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.6585403
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.60124.338136
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.39315486
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.9061516
X-RAY DIFFRACTIONr_chiral_restr0.110.2512
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0213610
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02640
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_it2.2263.9031648
X-RAY DIFFRACTIONr_mcbond_other2.2193.9021647
X-RAY DIFFRACTIONr_mcangle_it3.7495.8192039
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.8→2.87 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.407 76 -
Rwork0.254 652 -
obs--99.73 %

+
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