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- PDB-9oim: The von Hippel Lindau-ElonginB-ElonginC (VCB) complex with fragment 9 -

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Basic information

Entry
Database: PDB / ID: 9oim
TitleThe von Hippel Lindau-ElonginB-ElonginC (VCB) complex with fragment 9
Components
  • (Elongin-B) x 2
  • Elongin-C
  • von Hippel-Lindau disease tumor suppressor
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: 2.61 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)175,79916
Polymers174,97412
Non-polymers8254
Water1267
1
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,9244
Polymers43,7183
Non-polymers2061
Water362
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)43,9244
Polymers43,7183
Non-polymers2061
Water0
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)44,0284
Polymers43,8223
Non-polymers2061
Water181
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)43,9244
Polymers43,7183
Non-polymers2061
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)93.386, 93.386, 362.706
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
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 through 28 or (resid 29...
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 and (name N or name...
d_2ens_2(chain "E" and (resid 17 through 42 or (resid 43...
d_3ens_2(chain "H" and ((resid 17 and (name N or name...
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 68 or (resid 69...
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_1METMETGLUGLUAA1 - 591 - 59
d_12ens_1GLYGLYPHEPHEAA61 - 7961 - 79
d_13ens_1ASPASPMETMETAA83 - 10383 - 103
d_21ens_1METMETGLUGLUDD1 - 591 - 59
d_22ens_1GLYGLYMETMETDD61 - 10361 - 103
d_31ens_1METMETGLUGLUGG1 - 591 - 59
d_32ens_1GLYGLYPHEPHEGG61 - 7961 - 79
d_33ens_1ASPASPMETMETGG83 - 10383 - 103
d_41ens_1METMETGLUGLUJJ1 - 591 - 59
d_42ens_1GLYGLYPHEPHEJJ61 - 7961 - 79
d_43ens_1ASPASPMETMETJJ83 - 10383 - 103
d_11ens_2METMETCYSCYSBB17 - 1123 - 98
d_12ens_2A1CBIA1CBIA1CBIA1CBIBM201
d_21ens_2METMETSERSEREE17 - 473 - 33
d_22ens_2ASNASNCYSCYSEE58 - 11244 - 98
d_23ens_2A1CBIA1CBIA1CBIA1CBIEN201
d_31ens_2METMETSERSERHH17 - 473 - 33
d_32ens_2ASNASNCYSCYSHH58 - 11244 - 98
d_33ens_2A1CBIA1CBIA1CBIA1CBIHO201
d_41ens_2METMETSERSERKK17 - 473 - 33
d_42ens_2ASNASNCYSCYSKK58 - 11244 - 98
d_43ens_2A1CBIA1CBIA1CBIA1CBIKP201
d_11ens_3VALVALTHRTHRCC62 - 20229 - 169
d_21ens_3VALVALTHRTHRFF62 - 20229 - 169
d_31ens_3VALVALTHRTHRII62 - 20229 - 169
d_41ens_3VALVALTHRTHRLL62 - 20229 - 169

NCS ensembles :
ID
ens_1
ens_2
ens_3

NCS oper:
IDCodeMatrixVector
1given(0.999764975685, -0.0216478009575, -0.00116880625123), (0.0216357667631, 0.999720982922, -0.00947891880013), (0.0013736778818, 0.00945140300429, 0.999954390955)47.2774138097, 4.15893734083, 0.0644615434322
2given(0.993854745402, 0.0394055443581, -0.10344055354), (-0.0418561028812, 0.99888955511, -0.0216269124947), (0.102473468246, 0.0258236280623, 0.994400486997)47.3217688197, -42.935973171, 1.48386689583
3given(0.996916655307, 0.0320683752459, -0.0716156524816), (-0.0339672429668, 0.999098706636, -0.0254558599023), (0.0707347777017, 0.0278099569799, 0.997107415235)0.970552451638, -47.1612445779, 1.28295222564
4given(0.999845593917, -0.0129404941448, -0.0118883109305), (0.0129360785066, 0.999916224962, -0.000448251819625), (0.0118931155869, 0.000294394483309, 0.999929231063)46.9484242157, 4.46222344772, 0.186788204988
5given(0.991715912574, 0.0389756489909, -0.122394638499), (-0.0440835976874, 0.998254329344, -0.0393056021485), (0.120649016417, 0.0443755871067, 0.991702890036)46.5367773227, -43.4578206524, 1.54617561521
6given(0.995991681816, 0.0332490920136, -0.0830365439634), (-0.0372070572273, 0.998221317351, -0.0465815036133), (0.0813400556036, 0.0494843355685, 0.995457229562)0.39268634177, -47.9521916628, 1.27929928902
7given(0.999538398086, 0.0212038197974, -0.0217574993344), (-0.021255454386, 0.999771777024, -0.00214465036944), (0.0217070589932, 0.00260612592938, 0.999760977283)47.0381269601, 4.27760420841, 0.219383323228
8given(0.996816076757, 0.0543462952827, -0.0583454309141), (-0.0562134076583, 0.997942037338, -0.0308503308439), (0.0565487570062, 0.0340319012515, 0.997819656941)47.7787654386, -43.1879641386, 1.23210340734
9given(0.997470517825, 0.058890044415, -0.0398061394508), (-0.0604599017361, 0.997390499877, -0.0394561913631), (0.0373786884632, 0.0417630629101, 0.998428104685)1.29524697318, -47.8294988892, 1.19585202702

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Components

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Protein , 4 types, 12 molecules ADJBEHKCFILG

#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: 11852.389 Da / Num. of mol.: 3
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
#3: Protein
von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 20833.514 Da / Num. of mol.: 4
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 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: 11956.372 Da / Num. of mol.: 1
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

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Non-polymers , 2 types, 11 molecules

#5: Chemical
ChemComp-A1CBI / 1-[5-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]-2,3-dihydroindol-1-yl]ethanone


Mass: 206.198 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H10N2O3 / Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 7 / 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: 2.26 Å3/Da / Density % sol: 45.57 %
Crystal growTemperature: 293 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 PILATUS3 2M / Detector: PIXEL / Date: May 4, 2024
RadiationMonochromator: Double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.61→48.83 Å / Num. obs: 88336 / % possible obs: 95.8 % / Redundancy: 1.9 % / Biso Wilson estimate: 59.54 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.072 / Net I/σ(I): 10.6
Reflection shellResolution: 2.61→2.7 Å / Rmerge(I) obs: 1.01 / Mean I/σ(I) obs: 0.7 / Num. unique obs: 47542 / CC1/2: 0.458 / Rpim(I) all: 1.01 / % possible all: 97

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Processing

Software
NameVersionClassification
PHENIX1.21.2_5419refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.61→48.83 Å / SU ML: 0.4242 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 31.6025
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2833 2333 4.93 %
Rwork0.225 44987 -
obs0.2278 47320 94.42 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 62.08 Å2
Refinement stepCycle: LAST / Resolution: 2.61→48.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10298 0 60 7 10365
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.009810598
X-RAY DIFFRACTIONf_angle_d1.222714442
X-RAY DIFFRACTIONf_chiral_restr0.0631667
X-RAY DIFFRACTIONf_plane_restr0.01071863
X-RAY DIFFRACTIONf_dihedral_angle_d17.18513853
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAX-RAY DIFFRACTIONTorsion NCS0.591256313627
ens_1d_3AAX-RAY DIFFRACTIONTorsion NCS0.647734583809
ens_1d_4AAX-RAY DIFFRACTIONTorsion NCS0.592254573982
ens_2d_2BBX-RAY DIFFRACTIONTorsion NCS0.729402654275
ens_2d_3BBX-RAY DIFFRACTIONTorsion NCS0.977365163338
ens_2d_4BBX-RAY DIFFRACTIONTorsion NCS0.904743869245
ens_3d_2CCX-RAY DIFFRACTIONTorsion NCS0.738944137252
ens_3d_3CCX-RAY DIFFRACTIONTorsion NCS0.766617914541
ens_3d_4CCX-RAY DIFFRACTIONTorsion NCS0.72480307188
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.61-2.660.39511430.38712541X-RAY DIFFRACTION92.71
2.66-2.720.37781320.32182627X-RAY DIFFRACTION96.2
2.72-2.780.37891460.31362651X-RAY DIFFRACTION96.42
2.78-2.850.33621550.30882629X-RAY DIFFRACTION96.4
2.85-2.930.35391370.28322657X-RAY DIFFRACTION96.21
2.93-3.020.36491520.26962639X-RAY DIFFRACTION96.08
3.02-3.110.30461440.26742638X-RAY DIFFRACTION95.86
3.11-3.230.32651240.26022654X-RAY DIFFRACTION95.63
3.23-3.360.31021290.25422643X-RAY DIFFRACTION95.39
3.36-3.510.31451330.25422629X-RAY DIFFRACTION94.88
3.51-3.690.3191490.25572620X-RAY DIFFRACTION94.25
3.69-3.920.26611280.23152623X-RAY DIFFRACTION93.44
3.92-4.230.25141190.18362673X-RAY DIFFRACTION94.26
4.23-4.650.21061570.16052629X-RAY DIFFRACTION93.65
4.65-5.320.23341210.17892672X-RAY DIFFRACTION93.47
5.32-6.70.29661210.22482719X-RAY DIFFRACTION92.45
6.71-48.830.25411430.19062743X-RAY DIFFRACTION88.72
Refinement TLS params.Method: refined / Origin x: 12.0185218271 Å / Origin y: -29.2714841832 Å / Origin z: -23.6818176067 Å
111213212223313233
T0.68605414381 Å20.017152611801 Å2-0.0460430477615 Å2-0.430232101255 Å2-0.00442979346089 Å2--0.455998691646 Å2
L0.087318972307 °20.0360962252365 °2-0.0449613313614 °2-0.156413163924 °20.0240766707394 °2---0.0733571399047 °2
S0.0340436552086 Å °0.0120484602831 Å °-0.0209124020519 Å °-0.0288108183659 Å °-0.0302211196658 Å °-0.038368728448 Å °0.000599791676186 Å °0.0235545926656 Å °-0.00469832298665 Å °
Refinement TLS groupSelection details: all

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