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- PDB-4tqb: The co-complex structure of the translation initiation factor eIF... -

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Basic information

Entry
Database: PDB / ID: 4tqb
TitleThe co-complex structure of the translation initiation factor eIF4E with the inhibitor 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G
ComponentsEukaryotic translation initiation factor 4E
KeywordsPROTEIN BINDING / eIF4E / translation initiation inhibitor / allosteric / 4EGI1
Function / homology
Function and homology information


eukaryotic initiation factor 4G binding / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / regulation of translation at postsynapse, modulating synaptic transmission / RNA cap binding / chromatoid body / eukaryotic translation initiation factor 4F complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / mRNA cap binding / Deadenylation of mRNA / RNA 7-methylguanosine cap binding ...eukaryotic initiation factor 4G binding / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / regulation of translation at postsynapse, modulating synaptic transmission / RNA cap binding / chromatoid body / eukaryotic translation initiation factor 4F complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / mRNA cap binding / Deadenylation of mRNA / RNA 7-methylguanosine cap binding / Transport of the SLBP independent Mature mRNA / Transport of the SLBP Dependant Mature mRNA / M-decay: degradation of maternal mRNAs by maternally stored factors / Transport of Mature mRNA Derived from an Intronless Transcript / RISC complex / Ribosomal scanning and start codon recognition / stem cell population maintenance / Translation initiation complex formation / mTORC1-mediated signalling / negative regulation of neuron differentiation / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / behavioral fear response / mRNA export from nucleus / translation initiation factor activity / positive regulation of mitotic cell cycle / cellular response to dexamethasone stimulus / translational initiation / P-body / neuron differentiation / ISG15 antiviral mechanism / cytoplasmic ribonucleoprotein granule / cytoplasmic stress granule / G1/S transition of mitotic cell cycle / regulation of translation / DNA-binding transcription factor binding / postsynapse / negative regulation of translation / nuclear speck / glutamatergic synapse / perinuclear region of cytoplasm / enzyme binding / RNA binding / extracellular exosome / nucleus / cytosol / cytoplasm
Similarity search - Function
RNA Cap, Translation Initiation Factor Eif4e / RNA Cap, Translation Initiation Factor Eif4e / Eukaryotic translation initiation factor 4E (eIF-4E), conserved site / Eukaryotic initiation factor 4E signature. / Translation Initiation factor eIF- 4e / Eukaryotic initiation factor 4E / Translation Initiation factor eIF- 4e-like / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-34K / 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE / Eukaryotic translation initiation factor 4E
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.59 Å
AuthorsPapadopoulos, E. / Jenni, S. / Wagner, G.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2014
Title: Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.
Authors: Papadopoulos, E. / Jenni, S. / Kabha, E. / Takrouri, K.J. / Yi, T. / Salvi, N. / Luna, R.E. / Gavathiotis, E. / Mahalingam, P. / Arthanari, H. / Rodriguez-Mias, R. / Yefidoff-Freedman, R. / ...Authors: Papadopoulos, E. / Jenni, S. / Kabha, E. / Takrouri, K.J. / Yi, T. / Salvi, N. / Luna, R.E. / Gavathiotis, E. / Mahalingam, P. / Arthanari, H. / Rodriguez-Mias, R. / Yefidoff-Freedman, R. / Aktas, B.H. / Chorev, M. / Halperin, J.A. / Wagner, G.
History
DepositionJun 10, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 13, 2014Provider: repository / Type: Initial release
Revision 1.1Oct 1, 2014Group: Database references
Revision 2.0Dec 27, 2023Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Other / Refinement description / Source and taxonomy
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp_atom / chem_comp_bond / citation / database_2 / entity_src_gen / pdbx_database_status / pdbx_struct_oper_list / pdbx_validate_close_contact / pdbx_validate_symm_contact / refine_hist
Item: _atom_site.id / _atom_site_anisotrop.id ..._atom_site.id / _atom_site_anisotrop.id / _citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_oper_list.symmetry_operation / _pdbx_validate_symm_contact.auth_asym_id_1 / _pdbx_validate_symm_contact.auth_seq_id_1 / _pdbx_validate_symm_contact.auth_seq_id_2 / _pdbx_validate_symm_contact.dist / _pdbx_validate_symm_contact.site_symmetry_2

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Eukaryotic translation initiation factor 4E
B: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,3166
Polymers44,5812
Non-polymers1,7354
Water10,701594
1
A: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,4864
Polymers22,2901
Non-polymers1,1963
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,8302
Polymers22,2901
Non-polymers5391
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)39.830, 73.480, 66.260
Angle α, β, γ (deg.)90.00, 106.66, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein Eukaryotic translation initiation factor 4E / eIF4E / eIF-4F 25 kDa subunit / mRNA cap-binding protein


Mass: 22290.334 Da / Num. of mol.: 2 / Fragment: UNP residues 28-217
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4E, EIF4EL1, EIF4F / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: P06730
#2: Chemical ChemComp-MGT / 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE


Mass: 539.223 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C11H20N5O14P3
#3: Chemical ChemComp-34K / (2E)-2-{2-[4-(4-bromophenyl)-1,3-thiazol-2-yl]hydrazinylidene}-3-(2-nitrophenyl)propanoic acid


Mass: 461.289 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H13BrN4O4S
#4: Chemical ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID


Mass: 195.237 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C6H13NO4S / Comment: pH buffer*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 594 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 2.08 Å3/Da / Density % sol: 40.97 %
Crystal growTemperature: 290 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: PEG 4000 12-20%, 100mM MES pH 6.5, 10% IPN

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Data collection

DiffractionMean temperature: 80 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.91956 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 2, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91956 Å / Relative weight: 1
ReflectionResolution: 1.59→19.39 Å / Num. obs: 46347 / % possible obs: 94.1 % / Redundancy: 2.14 % / Net I/σ(I): 14.1

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Processing

SoftwareName: PHENIX / Version: (phenix.refine: 1.9_1692) / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.59→19.39 Å / SU ML: 0.23 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 23.85 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2109 2021 4.36 %
Rwork0.1819 --
obs0.1832 46338 94.27 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.59→19.39 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3032 0 106 594 3732
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0093396
X-RAY DIFFRACTIONf_angle_d1.1714638
X-RAY DIFFRACTIONf_dihedral_angle_d13.481267
X-RAY DIFFRACTIONf_chiral_restr0.043482
X-RAY DIFFRACTIONf_plane_restr0.006582
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.59-1.62980.45681380.39382744X-RAY DIFFRACTION82
1.6298-1.67380.3281370.33013092X-RAY DIFFRACTION93
1.6738-1.7230.30131430.28363108X-RAY DIFFRACTION94
1.723-1.77860.26171450.23473164X-RAY DIFFRACTION95
1.7786-1.84210.24621460.21753191X-RAY DIFFRACTION95
1.8421-1.91580.26791400.20813189X-RAY DIFFRACTION95
1.9158-2.00290.24291470.19453227X-RAY DIFFRACTION96
2.0029-2.10840.21411440.17033227X-RAY DIFFRACTION96
2.1084-2.24030.18161460.16273233X-RAY DIFFRACTION97
2.2403-2.4130.19331470.16443215X-RAY DIFFRACTION96
2.413-2.65530.19331480.16573261X-RAY DIFFRACTION96
2.6553-3.03830.17361460.16683260X-RAY DIFFRACTION97
3.0383-3.82310.16911470.15443231X-RAY DIFFRACTION96
3.8231-19.39240.21721470.16753175X-RAY DIFFRACTION93
Refinement TLS params.

Method: refined / 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)
15.7223-0.14312.11242.7795-0.30284.9405-0.0010.1310.3153-0.1021-0.05120.1866-0.106-0.09810.09140.1526-0.00390.06560.10510.01520.11435.9799-4.194-0.5025
25.68014.8097.17536.87645.17489.4429-0.10260.22050.6607-0.0198-0.23550.30750.17770.12320.30830.12290.04070.00860.18960.01220.1381-0.0868-0.6524-4.805
34.5055-0.6841-0.41633.3647-0.16137.5484-0.1536-0.00680.3444-0.23470.0221-0.0556-0.34510.03040.10010.095-0.0114-0.01190.10460.01490.115511.2297-1.94358.6176
44.04872.01641.37494.21050.86453.429-0.0744-0.25380.2649-0.2799-0.26891.3515-0.2917-0.59010.470.24970.1218-0.02040.3095-0.0410.3554-4.9527-3.07789.6721
54.36860.74711.28262.58290.86585.99930.2610.36010.2228-0.6361-0.1460.2379-0.0813-0.22670.07290.2610.0449-0.020.16860.03440.13133.4565-9.0519-5.46
67.1472-1.3756-2.75795.99240.43473.1324-0.03541.27640.1613-1.80610.1826-0.5989-0.25850.8343-0.31370.5871-0.0090.01010.3718-0.01720.18768.4324-15.9299-14.0557
74.3436-2.8154-3.48775.58361.91197.5835-0.1402-0.4699-0.27480.11080.11990.9977-0.0655-0.5150.04730.2075-0.0366-0.03590.32670.03050.3165-5.1745-18.6987.4812
85.2562-0.8583-2.45544.87030.19645.98790.0383-0.1606-0.15460.03110.13630.14850.319-0.2055-0.09410.114-0.0249-0.02420.12240.02430.09346.2701-14.15459.4497
95.7379-5.4893.05485.257-2.93632.2296-0.10190.2251-0.1849-0.3939-0.448-0.64660.21011.12040.64260.22480.05850.05610.3138-0.00970.349117.6837-21.32530.4229
103.2293-1.0507-0.8793.8822-0.00353.88570.12510.0601-0.2564-0.2917-0.10510.39270.2336-0.33050.04770.174-0.0313-0.04770.1823-0.00630.1154-0.1916-15.50920.1697
115.96312.02031.57840.69350.64214.81890.26530.2476-0.4738-0.82070.053-0.329-0.03270.4558-0.80280.53760.1221-0.06460.3455-0.14550.306210.6597-27.4484-8.4593
127.96641.639-5.38917.33570.83345.33980.0441-0.1728-0.4893-0.0396-0.1888-0.35650.4430.3998-0.04370.19710.0055-0.06420.1421-0.01770.19319.4638-26.01923.4212
135.06243.192-4.99248.4207-0.85467.30760.3493-0.1911-0.677-0.1377-0.2158-0.0321-0.45030.4362-0.08230.2568-0.0377-0.09740.17830.02650.1576.8408-22.775611.8909
146.72140.2754-2.94522.2728-1.24067.65270.1173-0.0478-0.1724-0.220.24750.54850.4555-0.6467-0.0870.3154-0.0358-0.06210.1523-0.01040.2132-0.3422-28.38114.7375
152.5103-1.79723.27864.4975-0.94775.82250.15610.3326-0.5366-1.1109-0.07830.98740.4023-0.86031.14670.52880.0305-0.2040.3238-0.12890.2868-3.4457-22.0613-11.5425
162.20320.9779-1.73096.4286-0.99989.319-0.28020.46880.4892-0.65850.09691.3801-0.6442-1.03370.5610.5152-0.0607-0.25370.3274-0.04550.4761-2.8907-27.7848-4.5033
178.2158-1.96821.44618.82454.293.55160.22440.4922-0.7483-0.2453-0.1095-0.61850.14150.1133-0.02160.18880.01620.06690.22830.03090.217821.4461-22.34715.194
187.1722-1.7766-3.11194.31110.77257.2438-0.0943-0.0453-0.4130.4186-0.0251-0.05620.3165-0.24990.09980.1266-0.0249-0.04020.08060.0170.130414.4894-19.04431.3903
192.54141.90194.12384.04423.62416.8018-0.2026-1.044-0.44280.38950.540.8546-0.4862-0.6026-0.57880.72790.06870.12550.81790.19470.513.7887-16.863847.4778
201.78030.5179-1.24591.8128-0.52145.51150.0074-0.0765-0.1570.2339-0.0462-0.0980.1202-0.0517-0.03050.1101-0.0207-0.00750.09870.01650.130812.2681-20.768328.4075
218.1127-5.9786-4.27945.93612.74395.5406-0.14690.1063-0.3380.4718-0.17490.76610.8002-0.76350.27820.2161-0.10630.02780.2567-0.02460.21841.8166-18.623125.6333
222.9828-0.53360.31023.19310.08043.25550.0394-0.2559-0.32980.4967-0.07810.19960.0441-0.3154-0.03410.1618-0.03460.01790.13760.02540.134810.9576-14.242334.246
230.8672-0.7884-0.97140.82711.54585.23790.0927-0.6345-0.29340.07350.1439-0.21510.33750.44741.39580.2511-0.0594-0.31850.24850.17020.181223.8917-11.597339.6096
246.35570.55242.34143.24470.10884.22010.0909-0.24140.00990.2695-0.0540.4439-0.0154-0.50630.02460.1715-0.01930.02040.1459-0.00230.14737.253-1.622530.3694
253.7045-1.0016-0.75753.866-0.08373.64550.00440.01480.03310.0392-0.030.1108-0.0303-0.11630.01550.0562-0.00940.00790.10490.00840.085412.1471-8.68421.6539
265.98684.1630.26786.0032-0.42327.3296-0.00710.6404-0.4226-0.28490.1431-0.96780.14591.22640.14590.137-0.0094-0.01420.2984-0.00430.292927.3551-5.364122.1282
275.1340.6907-0.08083.4247-0.20393.1433-0.0429-0.23690.18970.364-0.0223-0.0095-0.1433-0.115-0.02140.1483-0.0059-0.01430.09950.00240.080713.3859-5.921333.2917
288.1064-0.52171.45833.885-2.21231.4452-0.00980.16490.4260.3496-0.2294-0.5848-0.47770.44890.13140.1957-0.048-0.00890.16530.01920.186325.3942.457527.997
292.3677-3.515-2.37186.52614.91663.8911-0.0320.03760.3853-0.646-0.0949-0.2035-0.58460.02920.12550.1495-0.0125-0.02120.12070.01570.131515.34941.415720.4241
300.85781.48840.43932.8151.65254.0007-0.0371-0.05870.2840.0916-0.21580.3028-0.4154-0.33770.210.12990.02070.00040.1553-0.01560.137710.56355.512325.4199
317.1015.66531.83946.3505-1.23424.48140.265-0.71820.73761.0497-0.28930.5578-0.7342-0.38590.86530.4357-0.1002-0.02640.2788-0.02530.176716.7203-0.38442.8573
325.8004-0.0952-0.16655.3453-2.17637.61050.1457-1.2403-0.10531.20690.07930.075-0.4462-0.5216-0.09010.5028-0.0105-0.05790.3593-0.00120.255215.37555.980338.3048
331.0673-1.0509-0.21791.1718-0.04920.55230.1672-0.3704-0.42090.1558-0.28610.88780.195-1.0465-0.04120.4531-0.0281-0.10.4459-0.05730.3678-7.3876-14.2448-6.9007
341.26782.4815-0.11574.9888-0.27360.03520.073-0.34760.39360.3344-0.11920.7792-0.1525-0.5956-0.02570.3692-0.05390.01080.3256-0.00280.21229.4619-7.183543.0566
350.13470.0435-0.09350.0852-0.01710.072-0.5830.1150.25320.12320.02110.20590.39480.4560.00170.54690.0726-0.06230.3332-0.01840.4627-4.01892.40810.9273
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(chain A and resid 33:57)
2X-RAY DIFFRACTION2(chain A and resid 58:64)
3X-RAY DIFFRACTION3(chain A and resid 65:78)
4X-RAY DIFFRACTION4(chain A and resid 79:87)
5X-RAY DIFFRACTION5(chain A and resid 88:104)
6X-RAY DIFFRACTION6(chain A and resid 105:109)
7X-RAY DIFFRACTION7(chain A and resid 110:124)
8X-RAY DIFFRACTION8(chain A and resid 125:141)
9X-RAY DIFFRACTION9(chain A and resid 142:147)
10X-RAY DIFFRACTION10(chain A and resid 148:168)
11X-RAY DIFFRACTION11(chain A and resid 169:174)
12X-RAY DIFFRACTION12(chain A and resid 175:184)
13X-RAY DIFFRACTION13(chain A and resid 185:189)
14X-RAY DIFFRACTION14(chain A and resid 190:198)
15X-RAY DIFFRACTION15(chain A and resid 199:206)
16X-RAY DIFFRACTION16(chain A and resid 207:217)
17X-RAY DIFFRACTION17(chain B and resid 35:40)
18X-RAY DIFFRACTION18(chain B and resid 41:49)
19X-RAY DIFFRACTION19(chain B and resid 50:55)
20X-RAY DIFFRACTION20(chain B and resid 56:77)
21X-RAY DIFFRACTION21(chain B and resid 78:82)
22X-RAY DIFFRACTION22(chain B and resid 83:102)
23X-RAY DIFFRACTION23(chain B and resid 103:107)
24X-RAY DIFFRACTION24(chain B and resid 108:125)
25X-RAY DIFFRACTION25(chain B and resid 126:142)
26X-RAY DIFFRACTION26(chain B and resid 143:147)
27X-RAY DIFFRACTION27(chain B and resid 148:170)
28X-RAY DIFFRACTION28(chain B and resid 171:180)
29X-RAY DIFFRACTION29(chain B and resid 181:186)
30X-RAY DIFFRACTION30(chain B and resid 187:197)
31X-RAY DIFFRACTION31(chain B and resid 198:206)
32X-RAY DIFFRACTION32(chain B and resid 207:217)
33X-RAY DIFFRACTION33(chain A and resid 301)
34X-RAY DIFFRACTION34(chain B and resid 1000)
35X-RAY DIFFRACTION35(chain A and resid 302)

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  • 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

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