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- PDB-9oio: The von Hippel Lindau-ElonginB-ElonginC (VCB) complex with fragme... -

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Basic information

Entry
Database: PDB / ID: 9oio
TitleThe von Hippel Lindau-ElonginB-ElonginC (VCB) complex with fragments 9 and 14
Components
  • (von Hippel-Lindau disease tumor ...) x 2
  • Elongin-B
  • Elongin-C
KeywordsPROTEIN TRANSPORT / VHL / E3 ligase / Fragment-based drug discovery
Function / homology
Function and homology information


regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / VCB complex / elongin complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / intracellular membraneless organelle ...regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / VCB complex / elongin complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / intracellular membraneless organelle / Cul2-RING ubiquitin ligase complex / SUMOylation of ubiquitinylation proteins / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / Tat-mediated elongation of the HIV-1 transcript / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV-1 elongation complex containing HIV-1 Tat / negative regulation of signal transduction / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / protein serine/threonine kinase binding / RNA Polymerase II Pre-transcription Events / negative regulation of autophagy / transcription corepressor binding / positive regulation of cell differentiation / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / cell morphogenesis / Evasion by RSV of host interferon responses / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / microtubule cytoskeleton / regulation of gene expression / Replication of the SARS-CoV-2 genome / protein-containing complex assembly / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / DNA-binding transcription factor binding / cellular response to hypoxia / molecular adaptor activity / amyloid fibril formation / proteasome-mediated ubiquitin-dependent protein catabolic process / protein stabilization / protein ubiquitination / cilium / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / mitochondrion / proteolysis / nucleoplasm / nucleus / plasma membrane / cytosol
Similarity search - Function
von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Elongin-C / Elongin B ...von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Elongin-C / Elongin B / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / SKP1/BTB/POZ domain superfamily / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
: / : / von Hippel-Lindau disease tumor suppressor / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsAmporndanai, K. / Katinas, J.M. / Chopra, A. / Fesik, S.W.
Funding support United States, 1items
OrganizationGrant numberCountry
Other privateAWD00000788 United States
CitationJournal: Acs Med.Chem.Lett. / Year: 2025
Title: NMR-Based Fragment Screen of the von Hippel-Lindau Elongin C&B Complex
Authors: Amporndanai, K. / Katinas, J.M. / Chopra, A. / Kayode, O. / Vadukoot, A.K. / Waterson, A.G. / Fesik, S.W.
History
DepositionMay 6, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 9, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
D: Elongin-B
E: Elongin-C
F: von Hippel-Lindau disease tumor suppressor
G: Elongin-B
H: Elongin-C
I: von Hippel-Lindau disease tumor suppressor
J: Elongin-B
K: Elongin-C
L: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)176,14724
Polymers174,35012
Non-polymers1,79612
Water4,504250
1
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,9285
Polymers43,6143
Non-polymers3142
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
D: Elongin-B
E: Elongin-C
F: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,2127
Polymers43,6143
Non-polymers5994
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
G: Elongin-B
H: Elongin-C
I: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,8726
Polymers43,5103
Non-polymers3623
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
J: Elongin-B
K: Elongin-C
L: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,1346
Polymers43,6143
Non-polymers5213
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)92.904, 92.904, 359.384
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number91
Space group name H-MP4122
Space group name HallP4w2c
Symmetry operation#1: x,y,z
#2: -y,x,z+1/4
#3: y,-x,z+3/4
#4: x,-y,-z+1/2
#5: -x,y,-z
#6: -x,-y,z+1/2
#7: y,x,-z+3/4
#8: -y,-x,-z+1/4
Components on special symmetry positions
IDModelComponents
11G-202-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and ((resid 1 and (name N or name...
d_2ens_1(chain "D" and ((resid 1 and (name N or name...
d_3ens_1(chain "G" and (resid 1 through 8 or (resid 9...
d_4ens_1(chain "J" and ((resid 1 and (name N or name...
d_1ens_2(chain "B" and (resid 17 through 33 or (resid 34...
d_2ens_2(chain "E" and (resid 17 through 33 or (resid 34...
d_3ens_2(chain "H" and (resid 17 through 42 or (resid 43...
d_4ens_2(chain "K" and (resid 17 through 42 or (resid 43...
d_1ens_3(chain "C" and ((resid 62 and (name N or name...
d_2ens_3(chain "F" and (resid 62 through 76 or resid 78...
d_3ens_3(chain "I" and (resid 62 through 63 or (resid 64...
d_4ens_3(chain "L" and (resid 62 through 63 or (resid 64...

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ens_1METMETPHEPHEAA1 - 791 - 79
d_12ens_1PHEPHEMETMETAA85 - 10385 - 103
d_21ens_1METMETMETMETDD1 - 1031 - 103
d_31ens_1METMETPHEPHEGG1 - 791 - 79
d_32ens_1PHEPHEMETMETGG85 - 10385 - 103
d_41ens_1METMETPHEPHEJJ1 - 791 - 79
d_42ens_1PHEPHEMETMETJJ85 - 10385 - 103
d_11ens_2METMETARGARGBB17 - 633 - 49
d_12ens_2ILEILETYRTYRBB65 - 8351 - 69
d_13ens_2ILEILECYSCYSBB90 - 11276 - 98
d_21ens_2METMETSERSEREE17 - 473 - 33
d_22ens_2ASNASNARGARGEE58 - 6344 - 49
d_23ens_2ILEILETYRTYREE65 - 8351 - 69
d_24ens_2ILEILECYSCYSEE90 - 11276 - 98
d_31ens_2METMETSERSERHH17 - 473 - 33
d_32ens_2ASNASNARGARGHH58 - 6344 - 49
d_33ens_2ILEILETYRTYRHH65 - 8351 - 69
d_34ens_2ILEILECYSCYSHH90 - 11276 - 98
d_41ens_2METMETSERSERKK17 - 473 - 33
d_42ens_2ASNASNARGARGKK58 - 6344 - 49
d_43ens_2ILEILECYSCYSKK65 - 11251 - 98
d_11ens_3VALVALPHEPHECC62 - 7629 - 43
d_12ens_3ASNASNPROPROCC78 - 17245 - 139
d_13ens_3ASNASNTHRTHRCC174 - 202141 - 169
d_14ens_3DMSDMSDMSDMSCN302
d_21ens_3VALVALPHEPHEFF62 - 7629 - 43
d_22ens_3ASNASNPROPROFF78 - 17245 - 139
d_23ens_3ASNASNTHRTHRFF174 - 202141 - 169
d_24ens_3DMSDMSDMSDMSFR303
d_31ens_3VALVALPHEPHEII62 - 7629 - 43
d_32ens_3ASNASNPROPROII78 - 17245 - 139
d_33ens_3ASNASNTHRTHRII174 - 202141 - 169
d_34ens_3DMSDMSDMSDMSIU301
d_41ens_3VALVALPHEPHELL62 - 7629 - 43
d_42ens_3ASNASNPROPROLL78 - 17245 - 139
d_43ens_3ASNASNTHRTHRLL174 - 202141 - 169
d_44ens_3DMSDMSDMSDMSLX302

NCS ensembles :
ID
ens_1
ens_2
ens_3

NCS oper:
IDCodeMatrixVector
1given(0.999271785861, -0.0380630098291, -0.00266557021779), (0.0380808669118, 0.999250116667, 0.00700370732957), (0.00239698917019, -0.00710011435557, 0.999971921015)46.633377991, 4.75867731843, -0.0946755201065
2given(0.993582137669, 0.0343313924017, -0.107777043942), (-0.03667530759, 0.999130251237, -0.0198409394169), (0.107002137914, 0.0236663592369, 0.99397708521)46.5594810034, -42.8760901497, 1.67329213961
3given(0.997059083984, 0.0221458058067, -0.0733672020009), (-0.0247297796221, 0.999098670017, -0.0345005154918), (0.0725370322257, 0.0362134071102, 0.996708065635)0.562436988994, -47.3000418904, 1.47205906139
4given(0.999516486965, -0.0303552908429, -0.00673413714757), (0.0303934456083, 0.999522112796, 0.00563777399423), (0.00655978272029, -0.00583972168813, 0.999961432707)46.4970046694, 4.68301886088, -0.0453189873024
5given(0.991004508577, 0.0199230331028, -0.132337208417), (-0.0250672608719, 0.998988898333, -0.0373204158526), (0.131459866165, 0.0403020316983, 0.990501918135)45.7204448926, -43.3677512288, 1.849607206
6given(0.995302801174, 0.0151543782417, -0.0956173561387), (-0.0200545421002, 0.998522864791, -0.0504965724592), (0.0947108722164, 0.0521769423126, 0.99413651848)-0.266673391305, -47.8075230181, 1.63513472788
7given(0.999640674346, 0.00473267662738, -0.0263841612435), (-0.0046298733263, 0.999981456482, 0.00395613003992), (0.0264023950725, -0.00383255317653, 0.999644049185)46.4139709275, 4.44551234088, 0.0260846030748
8given(0.996630256475, 0.0395380224099, -0.0718670763479), (-0.0422080526658, 0.998459300968, -0.0360208911811), (0.0703321560102, 0.0389328793597, 0.996763572135)46.9122566958, -43.36297162, 1.5317296173
9given(0.998248346536, 0.0333887562213, -0.0488408599124), (-0.0356799946536, 0.99826599902, -0.0468180860487), (0.0471929721517, 0.0484787186066, 0.997708693568)0.574393138334, -47.6709023532, 1.4636938422

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Components

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Protein , 2 types, 8 molecules ADGJBEHK

#1: Protein
Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


Mass: 11748.406 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370
#2: Protein
Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


Mass: 11031.668 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369

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Von Hippel-Lindau disease tumor ... , 2 types, 4 molecules CFLI

#3: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 20833.514 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / References: UniProt: P40337
#4: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 20729.531 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / References: UniProt: P40337

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Non-polymers , 4 types, 262 molecules

#5: Chemical ChemComp-A1CBL / 1-[(2-fluorophenyl)methyl]-4-(propan-2-yl)piperazine


Mass: 236.328 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C14H21FN2 / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#7: Chemical ChemComp-A1CBK / 1-[6-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]-2,3-dihydroindol-1-yl]ethanone


Mass: 206.198 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C10H10N2O3 / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 250 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.22 Å3/Da / Density % sol: 44.69 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.1 M sodium cacodylate pH 5.5, 0.2 M magnesium acetate, 5 mM DTT and 14-20% PEG8000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.2 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: May 4, 2024
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→48.49 Å / Num. obs: 71258 / % possible obs: 99.88 % / Redundancy: 26.5 % / Biso Wilson estimate: 50.12 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.1191 / Rpim(I) all: 0.0236 / Net I/σ(I): 19.12
Reflection shellResolution: 2.3→2.33 Å / Redundancy: 28 % / Rmerge(I) obs: 2.022 / Mean I/σ(I) obs: 2.03 / Num. unique obs: 2699 / CC1/2: 0.724 / Rpim(I) all: 0.387 / % possible all: 99.96

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Processing

Software
NameVersionClassification
PHENIX1.21.1_5286refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→48.49 Å / SU ML: 0.2763 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.6225
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2493 3591 5.05 %
Rwork0.2112 67584 -
obs0.2132 71175 99.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 59.36 Å2
Refinement stepCycle: LAST / Resolution: 2.3→48.49 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10381 0 120 250 10751
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.009110755
X-RAY DIFFRACTIONf_angle_d1.112114625
X-RAY DIFFRACTIONf_chiral_restr0.05981658
X-RAY DIFFRACTIONf_plane_restr0.01041912
X-RAY DIFFRACTIONf_dihedral_angle_d18.33634027
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAX-RAY DIFFRACTIONTorsion NCS0.673415839356
ens_1d_3AAX-RAY DIFFRACTIONTorsion NCS0.642182070728
ens_1d_4AAX-RAY DIFFRACTIONTorsion NCS0.642376770862
ens_2d_2BBX-RAY DIFFRACTIONTorsion NCS0.656958653924
ens_2d_3BBX-RAY DIFFRACTIONTorsion NCS0.803387972259
ens_2d_4BBX-RAY DIFFRACTIONTorsion NCS0.726541092462
ens_3d_2CCX-RAY DIFFRACTIONTorsion NCS1.0136156588
ens_3d_3CCX-RAY DIFFRACTIONTorsion NCS1.92403498025
ens_3d_4CCX-RAY DIFFRACTIONTorsion NCS0.754525285737
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.330.31541230.26872576X-RAY DIFFRACTION100
2.33-2.360.34021420.27832542X-RAY DIFFRACTION99.96
2.36-2.40.28791170.26522578X-RAY DIFFRACTION100
2.4-2.430.36581280.27162578X-RAY DIFFRACTION99.96
2.43-2.470.32421470.27172523X-RAY DIFFRACTION100
2.47-2.510.32481390.26432583X-RAY DIFFRACTION99.85
2.51-2.550.31631190.25822537X-RAY DIFFRACTION100
2.55-2.60.31841310.25162580X-RAY DIFFRACTION100
2.6-2.650.34331300.25852561X-RAY DIFFRACTION99.96
2.65-2.70.29111390.24722546X-RAY DIFFRACTION100
2.7-2.760.28931320.24742577X-RAY DIFFRACTION99.96
2.76-2.830.30031300.24272581X-RAY DIFFRACTION99.96
2.83-2.90.30791560.23812565X-RAY DIFFRACTION100
2.9-2.980.27091400.22722559X-RAY DIFFRACTION99.85
2.98-3.060.29671220.22722596X-RAY DIFFRACTION99.93
3.06-3.160.25421170.22382607X-RAY DIFFRACTION99.96
3.16-3.280.24331690.21382546X-RAY DIFFRACTION99.85
3.28-3.410.25851540.22122592X-RAY DIFFRACTION99.96
3.41-3.560.2791490.21222605X-RAY DIFFRACTION99.89
3.56-3.750.27351260.21322615X-RAY DIFFRACTION99.93
3.75-3.980.21821480.18612613X-RAY DIFFRACTION99.93
3.98-4.290.2261360.17382622X-RAY DIFFRACTION99.89
4.29-4.720.20311450.17182651X-RAY DIFFRACTION99.89
4.72-5.410.22591450.18952668X-RAY DIFFRACTION99.79
5.41-6.810.2691440.23662716X-RAY DIFFRACTION99.9
6.81-48.490.18811630.19012867X-RAY DIFFRACTION98.57
Refinement TLS params.Method: refined / Origin x: 11.8709738076 Å / Origin y: -29.7391782204 Å / Origin z: -23.3660171821 Å
111213212223313233
T0.545442454986 Å20.00677856917295 Å2-0.0902781153041 Å2-0.353713347819 Å20.0185779179745 Å2--0.408942723431 Å2
L0.139844564986 °20.00611857023414 °2-0.0310140318809 °2-0.00323682578703 °20.0444187191732 °2---0.0327456119668 °2
S0.0236319576317 Å °0.0163279789877 Å °0.00631778301901 Å °-0.0237251127654 Å °-0.015737808812 Å °-0.00497788580353 Å °0.0160287770045 Å °0.0043398067101 Å °2.14274580204E-5 Å °
Refinement TLS groupSelection details: all

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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

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