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- PDB-9hyb: CRYSTAL STRUCTURE OF THE SMARCA2-VCB-COMPLEX WITH PROTAC P3 -

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Basic information

Entry
Database: PDB / ID: 9hyb
TitleCRYSTAL STRUCTURE OF THE SMARCA2-VCB-COMPLEX WITH PROTAC P3
Components
  • Elongin-B
  • Elongin-C
  • Probable global transcription activator SNF2L2
  • von Hippel-Lindau disease tumor suppressor
KeywordsLIGASE / BROMODOMAIN / VCB / E3-LIGASE
Function / homology
Function and homology information


bBAF complex / npBAF complex / regulation of cellular response to hypoxia / nBAF complex / brahma complex / nucleosome array spacer activity / negative regulation of receptor signaling pathway via JAK-STAT / RHOBTB3 ATPase cycle / GBAF complex / regulation of G0 to G1 transition ...bBAF complex / npBAF complex / regulation of cellular response to hypoxia / nBAF complex / brahma complex / nucleosome array spacer activity / negative regulation of receptor signaling pathway via JAK-STAT / RHOBTB3 ATPase cycle / GBAF complex / regulation of G0 to G1 transition / intermediate filament cytoskeleton / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / regulation of nucleotide-excision repair / Replication of the SARS-CoV-1 genome / VCB complex / SWI/SNF complex / regulation of mitotic metaphase/anaphase transition / Cul5-RING ubiquitin ligase complex / positive regulation of T cell differentiation / intracellular membraneless organelle / Cul2-RING ubiquitin ligase complex / positive regulation of double-strand break repair / SUMOylation of ubiquitinylation proteins / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / positive regulation of stem cell population maintenance / Regulation of MITF-M-dependent genes involved in pigmentation / regulation of G1/S transition of mitotic cell cycle / 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 / negative regulation of cell differentiation / spermatid development / positive regulation of myoblast differentiation / ATP-dependent activity, acting on DNA / negative regulation of signal transduction / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / ubiquitin-like ligase-substrate adaptor activity / 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 / RNA Polymerase II Pre-transcription Events / protein serine/threonine kinase binding / negative regulation of autophagy / transcription corepressor binding / TP53 Regulates Transcription of DNA Repair Genes / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / positive regulation of cell differentiation / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / helicase activity / Vif-mediated degradation of APOBEC3G / negative regulation of cell growth / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Regulation of expression of SLITs and ROBOs / RMTs methylate histone arginines / cell morphogenesis / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / nervous system development / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / microtubule cytoskeleton / regulation of gene expression / protein-containing complex assembly / Replication of the SARS-CoV-2 genome / ubiquitin-dependent protein catabolic process / histone binding / protein-macromolecule adaptor activity / cellular response to hypoxia / DNA-binding transcription factor binding / amyloid fibril formation / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / transcription coactivator activity / transcription cis-regulatory region binding / protein stabilization / hydrolase activity / cilium / protein ubiquitination / chromatin remodeling / negative regulation of cell population proliferation / negative regulation of gene expression / negative regulation of DNA-templated transcription / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / ubiquitin protein ligase binding / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process
Similarity search - Function
BRK domain / BRK domain / BRK domain superfamily / domain in transcription and CHROMO domain helicases / Glutamine-Leucine-Glutamine, QLQ / QLQ / QLQ domain profile. / QLQ / Snf2-ATP coupling, chromatin remodelling complex / Snf2, ATP coupling domain ...BRK domain / BRK domain / BRK domain superfamily / domain in transcription and CHROMO domain helicases / Glutamine-Leucine-Glutamine, QLQ / QLQ / QLQ domain profile. / QLQ / Snf2-ATP coupling, chromatin remodelling complex / Snf2, ATP coupling domain / Snf2-ATP coupling, chromatin remodelling complex / domain in helicases and associated with SANT domains / 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 / HSA domain / Helicase/SANT-associated domain / HSA domain profile. / Elongin-C / Elongin B / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / : / SNF2-like, N-terminal domain superfamily / SNF2, N-terminal / SNF2-related domain / SKP1/BTB/POZ domain superfamily / Helicase conserved C-terminal domain / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Ubiquitin-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
: / von Hippel-Lindau disease tumor suppressor / SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.84 Å
AuthorsBader, G. / Wolkerstorfer, B.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2025
Title: Frustration in the protein-protein interface plays a central role in the cooperativity of PROTAC ternary complexes.
Authors: Ma, N. / Bhattacharya, S. / Muk, S. / Jandova, Z. / Schmalhorst, P.S. / Ghosh, S. / Le, K. / Diers, E. / Trainor, N. / Farnaby, W. / Roy, M.J. / Kofink, C. / Greb, P. / Weinstabl, H. / ...Authors: Ma, N. / Bhattacharya, S. / Muk, S. / Jandova, Z. / Schmalhorst, P.S. / Ghosh, S. / Le, K. / Diers, E. / Trainor, N. / Farnaby, W. / Roy, M.J. / Kofink, C. / Greb, P. / Weinstabl, H. / Ciulli, A. / Bader, G. / Sankar, K. / Bergner, A. / Vaidehi, N.
History
DepositionJan 9, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 12, 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
M: Probable global transcription activator SNF2L2
N: Probable global transcription activator SNF2L2
O: Probable global transcription activator SNF2L2
P: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)227,88120
Polymers223,22316
Non-polymers4,6574
Water5,386299
1
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
P: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,9705
Polymers55,8064
Non-polymers1,1641
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
D: Elongin-B
E: Elongin-C
F: von Hippel-Lindau disease tumor suppressor
M: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,9705
Polymers55,8064
Non-polymers1,1641
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
G: Elongin-B
H: Elongin-C
I: von Hippel-Lindau disease tumor suppressor
O: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,9705
Polymers55,8064
Non-polymers1,1641
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
J: Elongin-B
K: Elongin-C
L: von Hippel-Lindau disease tumor suppressor
N: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,9705
Polymers55,8064
Non-polymers1,1641
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)108.378, 78.54, 171.575
Angle α, β, γ (deg.)90, 91.43, 90
Int Tables number4
Space group name H-MP1211

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Components

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Protein , 4 types, 16 molecules ADGJBEHKCFILMNOP

#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: 10974.616 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: 18702.291 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
Probable global transcription activator SNF2L2 / ATP-dependent helicase SMARCA2 / BRG1-associated factor 190B / BAF190B / Protein brahma homolog / ...ATP-dependent helicase SMARCA2 / BRG1-associated factor 190B / BAF190B / Protein brahma homolog / hBRM / SNF2-alpha / SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2


Mass: 14380.542 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SMARCA2, BAF190B, BRM, SNF2A, SNF2L2 / Production host: Escherichia coli (E. coli)
References: UniProt: P51531, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement

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Non-polymers , 2 types, 303 molecules

#5: Chemical
ChemComp-A1IYB / (2~{S},4~{R})-~{N}-[(1~{R})-2-[2-[4-[4-bromanyl-7-cyclopentyl-5-oxidanylidene-10-[[(2~{S})-oxolan-2-yl]methoxy]-6~{H}-benzimidazolo[1,2-a]quinazolin-9-yl]piperidin-1-yl]ethoxy]-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-1-[(2~{S})-2-[[1-(dimethylamino)cyclopropyl]carbonylamino]-3,3-dimethyl-butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide


Mass: 1164.278 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C60H77BrN9O8S / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 299 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationN

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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: 3.27 Å3/Da / Density % sol: 62.39 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.1 M Bis-Tris propane, 20 % PEG 3350, 0.2 M tri-sodium citrate

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99988 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Mar 22, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99988 Å / Relative weight: 1
ReflectionResolution: 2.86→108.34 Å / Num. obs: 42775 / % possible obs: 92.8 % / Redundancy: 4.4 % / CC1/2: 0.995 / Net I/σ(I): 8.6
Reflection shellResolution: 2.86→3.225 Å / Num. unique obs: 8971 / CC1/2: 0.602

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Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
Aimlessdata scaling
STARANISOdata scaling
BUSTERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.84→32.47 Å / Cor.coef. Fo:Fc: 0.867 / Cor.coef. Fo:Fc free: 0.852 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 0.513
RfactorNum. reflection% reflectionSelection details
Rfree0.265 2061 -RANDOM
Rwork0.251 ---
obs0.252 42742 62.1 %-
Displacement parametersBiso mean: 73.23 Å2
Baniso -1Baniso -2Baniso -3
1--1.924 Å20 Å20.6392 Å2
2--0.7982 Å20 Å2
3---1.1259 Å2
Refine analyzeLuzzati coordinate error obs: 0.56 Å
Refinement stepCycle: LAST / Resolution: 2.84→32.47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14697 0 316 299 15312
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.00830482HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.9255360HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d6795SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes4611HARMONIC5
X-RAY DIFFRACTIONt_it30482HARMONIC20
X-RAY DIFFRACTIONt_nbd1SEMIHARMONIC5
X-RAY DIFFRACTIONt_chiral_improper_torsion1975SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact30671SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion2.19
X-RAY DIFFRACTIONt_other_torsion20.61
LS refinement shellResolution: 2.84→3.08 Å
RfactorNum. reflection% reflection
Rfree0.3213 33 -
Rwork0.3154 --
obs0.3156 855 5.75 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
14.66010.57540.33590.57370.91051.957-0.0079-0.09020.0243-0.0902-0.01670.14220.02430.14220.0246-0.0472-0.14650.0362-0.0033-0.0871-0.163973.792236.737267.1244
20.32942.0749-1.39481.8065-1.50514.22440.00080.01820.09660.0182-0.03520.00250.09660.00250.03440.0641-0.0286-0.0534-0.16680.0119-0.080842.2698-6.238250.2842
31.3840.683-1.25460.5395-1.342.23270.00710.0535-0.03570.0535-0.0196-0.1047-0.0357-0.10470.0125-0.0437-0.15110.11960.07070.0656-0.1161.0343-11.941232.0663
41.2941-1.33720.46843.4007-0.12812.864-0.01370.05080.09060.05080.00840.13130.09060.13130.00530.144-0.00480.033-0.19830.0717-0.084242.0271-5.965668.1855
51.7623-0.9025-1.91572.82392.49451.6475-0.0091-0.0060.0231-0.0060.0201-0.08470.0231-0.0847-0.011-0.04580.14580.13830.0198-0.1034-0.216111.807537.651598.9953
61.33560.5366-0.2912.18280.35791.6889-0.02090.0708-0.02180.07080.0625-0.1223-0.0218-0.1223-0.04160.10830.04180.0779-0.10480.0698-0.235228.768214.264480.7233
71.33380.20162.82390.25070.51372.33420.0085-0.1052-0.0545-0.1052-0.0391-0.1364-0.0545-0.13640.0305-0.07030.1514-0.0708-0.015-0.0397-0.045110.656528.4855-3.1855
82.187-2.9165-0.47371.74191.24361.9411-0.01640.0059-0.00130.0059-0.0379-0.1574-0.0013-0.15740.05430.00290.115-0.0116-0.051-0.0322-0.004819.303232.826111.8513
91.9973-0.8747-0.30762.824-0.22731.43410.02180.03880.05190.03880.0051-0.10040.0519-0.1004-0.027-0.1319-0.0275-0.0411-0.0547-0.0201-0.007840.68217.184918.9731
101.11172.25091.00262.7392-0.91881.8022-0.0056-0.0786-0.1236-0.07860.0340.0286-0.12360.0286-0.0284-0.05550.00960.1416-0.0785-0.0628-0.073444.02577.3001-22.5412
113.5615-2.1451-2.60762.28440.44793.2334-0.0048-0.06450.0498-0.06450.0610.03950.04980.0395-0.0563-0.11440.0212-0.00590.013-0.1552-0.018340.7174-9.1558-15.9593
122.0158-0.0536-0.35922.1171.25821.86390.00820.10760.15210.1076-0.1069-0.0540.1521-0.0540.0987-0.166-0.0586-0.0191-0.0195-0.04430.101923.6313-10.00127.5191
131.35612.8066-1.03182.1635-1.71380.1244-0.0018-0.0378-0.0076-0.03780.016-0.1918-0.0076-0.1918-0.0141-0.0631-0.1270.00360.09410.1262-0.06755.389520.526445.9034
142.3256-1.3724-0.43551.65980.16940.771-0.01010.0731-0.02860.07310.0206-0.1075-0.0286-0.1075-0.01050.00610.01410.0091-0.02270.1335-0.02414.92935.711846.5142
151.2659-0.01320.49920.90540.45171.4499-0.00050.0959-0.03670.09590.11980.0814-0.03670.0814-0.11930.1249-0.08930.0251-0.11270.0143-0.089341.355735.159658.0616
164.3346-1.55770.53451.0324-0.80570.3709-0.0068-0.04530.0854-0.04530.0190.16120.08540.1612-0.0121-0.17220.0216-0.0310.02060.05080.006369.29291.157227.4178
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ N|* }
2X-RAY DIFFRACTION2{ A|* }
3X-RAY DIFFRACTION3{ O|* }
4X-RAY DIFFRACTION4{ B|* }
5X-RAY DIFFRACTION5{ P|* }
6X-RAY DIFFRACTION6{ C|* }
7X-RAY DIFFRACTION7{ D|* }
8X-RAY DIFFRACTION8{ E|* }
9X-RAY DIFFRACTION9{ F|* }
10X-RAY DIFFRACTION10{ G|* }
11X-RAY DIFFRACTION11{ H|* }
12X-RAY DIFFRACTION12{ I|* }
13X-RAY DIFFRACTION13{ J|* }
14X-RAY DIFFRACTION14{ K|* }
15X-RAY DIFFRACTION15{ L|* }
16X-RAY DIFFRACTION16{ M|* }

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