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

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Basic information

Entry
Database: PDB / ID: 4tpw
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 4EEIF4E
KeywordsPROTEIN BINDING / eIF4E / 4EGI1 / allosteric / translation initiation inhibitor
Function / homology
Function and homology information


Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic initiation factor 4G binding / 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 ...Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic initiation factor 4G binding / 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 / Transport of the SLBP independent Mature mRNA / Transport of the SLBP Dependant Mature mRNA / RNA 7-methylguanosine cap binding / 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 / Translation initiation complex formation / stem cell population maintenance / mTORC1-mediated signalling / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of neuron differentiation / L13a-mediated translational silencing of Ceruloplasmin expression / behavioral fear response / mRNA export from nucleus / translational initiation / translation initiation factor activity / cellular response to dexamethasone stimulus / positive regulation of mitotic cell cycle / P-body / G1/S transition of mitotic cell cycle / cytoplasmic ribonucleoprotein granule / ISG15 antiviral mechanism / neuron differentiation / cytoplasmic stress granule / regulation of translation / postsynapse / DNA-binding transcription factor binding / 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-33R / 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE / Eukaryotic translation initiation factor 4E
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsPapadopoulos, E. / Jenni, S. / Wagner, G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)CA68262 United States
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 9, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 13, 2014Provider: repository / Type: Initial release
Revision 1.1Oct 1, 2014Group: Database references
Revision 1.2Feb 4, 2015Group: Derived calculations
Revision 2.0Sep 6, 2017Group: Advisory / Atomic model ...Advisory / Atomic model / Author supporting evidence / Database references / Derived calculations / Other / Source and taxonomy
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / citation / entity_src_gen / pdbx_audit_support / pdbx_database_status / pdbx_struct_oper_list / pdbx_validate_close_contact / pdbx_validate_symm_contact
Item: _atom_site.id / _atom_site_anisotrop.id ..._atom_site.id / _atom_site_anisotrop.id / _citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag / _pdbx_audit_support.funding_organization / _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_asym_id_2 / _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
Revision 2.1Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 2.2Sep 27, 2023Group: 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 / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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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)46,3046
Polymers44,5812
Non-polymers1,7234
Water7,638424
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A: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,2803
Polymers22,2901
Non-polymers9892
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,0243
Polymers22,2901
Non-polymers7332
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)39.340, 73.200, 65.720
Angle α, β, γ (deg.)90.00, 106.25, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein Eukaryotic translation initiation factor 4E / EIF4E / 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-MGP / 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE


Mass: 538.215 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C11H19N5O14P3
#3: Chemical ChemComp-33R / (2E)-2-{2-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]hydrazinylidene}-3-(2-nitrophenyl)propanoic acid


Mass: 451.283 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H12Cl2N4O4S
#4: Chemical ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID / MES (buffer)


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 / Water


Mass: 18.015 Da / Num. of mol.: 424 / 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: 2.04 Å3/Da / Density % sol: 39.64 %
Crystal growTemperature: 290 K / Method: vapor diffusion, sitting drop / Details: PEG 4000 10-20%, 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: 0.97919 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: 0.97919 Å / Relative weight: 1
ReflectionResolution: 1.5→19.7 Å / Num. obs: 54446 / % possible obs: 95.15 % / Redundancy: 2.7 % / Net I/σ(I): 21.51
Reflection shellResolution: 1.5→1.53 Å / % possible all: 96

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Processing

SoftwareName: PHENIX / Version: (phenix.refine: 1.9_1692) / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1EJ1
Resolution: 1.5→19.666 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 23.82 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1928 2377 4.37 %
Rwork0.1716 --
obs0.1725 54437 95.15 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.5→19.666 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3032 0 107 424 3563
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0043327
X-RAY DIFFRACTIONf_angle_d0.8124543
X-RAY DIFFRACTIONf_dihedral_angle_d15.0581245
X-RAY DIFFRACTIONf_chiral_restr0.03470
X-RAY DIFFRACTIONf_plane_restr0.003568
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.5-1.53060.32931430.32483067X-RAY DIFFRACTION96
1.5306-1.56390.32791420.30383160X-RAY DIFFRACTION98
1.5639-1.60030.32521450.28173065X-RAY DIFFRACTION97
1.6003-1.64030.26711430.25773179X-RAY DIFFRACTION98
1.6403-1.68460.26271510.23793079X-RAY DIFFRACTION98
1.6846-1.73410.2761370.22733171X-RAY DIFFRACTION98
1.7341-1.79010.25181380.20993130X-RAY DIFFRACTION97
1.7901-1.8540.24151480.20123083X-RAY DIFFRACTION97
1.854-1.92820.18671340.19093113X-RAY DIFFRACTION97
1.9282-2.01580.23481340.17953086X-RAY DIFFRACTION96
2.0158-2.1220.18191390.16463059X-RAY DIFFRACTION95
2.122-2.25480.16851320.16123053X-RAY DIFFRACTION94
2.2548-2.42860.17151360.15483034X-RAY DIFFRACTION94
2.4286-2.67240.20231350.16543013X-RAY DIFFRACTION93
2.6724-3.05790.1661370.16512982X-RAY DIFFRACTION92
3.0579-3.84790.14881400.13932907X-RAY DIFFRACTION90
3.8479-19.66760.18761430.14822879X-RAY DIFFRACTION88
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)
15.26310.19842.38962.82650.43644.3276-0.085-0.01420.2638-0.2392-0.01190.0722-0.0556-0.05450.15330.1723-0.020.07010.15410.00440.15756.1028-4.304-0.5472
24.51793.01965.79455.91973.07397.7413-0.2250.17180.8789-0.3797-0.10950.2650.0384-0.10410.35750.23330.0154-0.01030.2230.02540.22230.099-0.6325-4.8745
33.0156-0.96641.50914.0050.44624.7997-0.1326-0.04130.2125-0.14490.1416-0.0981-0.11780.08620.01910.1328-0.01690.01980.16360.02160.177411.4158-2.06898.4005
43.37942.2283.20054.8879-0.64345.20490.0811-1.0569-0.19430.6097-0.4371.80730.2215-0.34570.38450.40320.08370.08780.6658-0.00180.6719-4.1881-1.777310.3507
57.97260.1882.01445.35380.20085.35040.12930.24280.1576-0.6399-0.04670.3347-0.2081-0.0427-0.14530.27350.0322-0.01830.16420.02850.18723.509-8.9911-5.4779
65.21472.9197-3.07068.1137-1.2891.9297-0.02680.65690.1777-1.15630.1802-0.6141-0.12130.3307-0.27750.51380.09430.04480.3336-0.03350.21548.2453-15.6413-13.9606
74.4905-1.6069-1.27995.30951.07084.62590.0705-0.7057-0.04160.4235-0.02390.96180.2212-0.53380.03570.3194-0.1020.06440.4602-0.03560.3965-5.0392-18.57897.5079
87.3673-0.8291-0.50224.91030.04064.30870.2513-0.14410.04540.1806-0.07460.07740.1916-0.1275-0.13440.1473-0.03580.00830.1580.00880.14956.4057-14.17869.3854
93.7801-3.5651.21673.6380.3568.7965-0.17640.237-0.3409-0.47940.006-0.48870.05891.57190.13270.30490.0580.02850.4012-0.05530.376317.74-21.48030.2562
105.1072-0.32320.55274.3897-0.03633.8560.0813-0.0515-0.1401-0.0265-0.10240.38430.3597-0.37510.0240.1798-0.0363-0.01270.1699-0.01120.1445-0.143-15.4370.1825
118.151-2.64280.99172.9967-2.59232.7660.68420.4834-0.7892-1.192-0.1945-0.0210.67440.6619-0.48240.59170.1089-0.00550.3915-0.09160.355610.4687-27.6217-8.4885
127.13971.3971-3.54644.17351.42233.08680.1431-0.1893-0.54220.104-0.2931-0.15030.3270.198-0.00280.31840.0111-0.05950.2052-0.00170.27779.4353-26.0523.3168
139.64713.9975-4.02192.14910.07158.55690.6156-0.5329-0.6540.5591-0.5268-0.0911-0.28930.3401-0.02590.3554-0.0881-0.08060.31210.02060.27096.8273-22.752411.8171
146.05981.2106-2.5334.3492-1.135.19630.205-0.3133-0.46880.2613-0.25150.21050.1083-0.2257-0.08640.4372-0.0593-0.08970.23870.00030.3296-0.4043-28.37964.7346
155.8329-0.31063.92332.4240.66482.95180.06880.4115-0.2634-1.4539-0.09421.22510.2353-0.82770.17520.51660.0103-0.18980.3954-0.080.3847-3.6508-22.0644-11.4472
167.1782-1.35731.0128.1162-3.75912.4759-0.2580.41070.1668-0.40080.04031.1675-0.8708-0.74170.16680.52760.0283-0.1470.3644-0.07640.4507-2.9612-27.7914-4.5154
172.4274-0.02442.12743.19974.38358.42790.12720.7742-0.28230.24340.2368-0.83170.27590.5505-0.32250.26440.07310.030.3057-0.01490.366321.5319-22.448215.0456
185.6428-1.4403-2.17744.74740.58876.24780.0501-0.1199-0.29220.4484-0.0746-0.0150.2506-0.08770.10260.2165-0.0315-0.03790.12780.02380.183514.5609-19.014831.1914
194.65270.82670.0572.37033.75359.5715-0.51180.23210.0649-0.01140.66361.0023-0.5268-0.7283-0.33490.92090.0240.13980.92110.10260.80053.8902-16.751447.1255
201.60550.3468-0.62251.6592-0.0934.62890.0727-0.0493-0.09930.15310.0151-0.04840.3621-0.0718-0.13630.2272-0.0287-0.01210.14080.01990.214412.373-20.770128.2664
216.1750.24540.84053.73332.9172.36590.2853-0.0897-0.64170.83780.07010.65261.3062-0.75180.39760.4721-0.1532-0.06120.3630.01450.35591.9373-18.578925.4031
222.1095-0.7187-0.00643.9565-0.15294.1893-0.0002-0.165-0.19680.54820.01060.18190.0612-0.2511-0.02380.2943-0.03430.01070.17470.05080.230811.0583-14.205334.0169
230.73630.0809-2.53665.402-1.02778.95760.0077-0.9956-0.51450.30620.1239-0.54770.16550.29010.2160.4231-0.0301-0.19270.32720.07480.340223.9804-11.525139.3883
244.92550.80581.85623.96020.21484.21830.0218-0.14060.25420.3403-0.10350.44430.0341-0.4710.00370.2431-0.01070.04650.2195-0.01060.23087.4351-1.579230.1705
252.2077-0.84230.27114.5406-0.15923.24460.02040.06060.08040.1179-0.0488-0.0879-0.039-0.02460.06330.1304-0.01560.02330.15060.00990.154512.2756-8.723821.4343
265.31387.0467-0.57299.3664-0.7984.70930.1510.6275-0.2656-0.23770.3138-0.80670.23581.0171-0.02010.1773-0.00130.00980.4153-0.03780.434927.4664-5.360621.9497
274.89710.26750.05174.57710.2083.9174-0.0828-0.30980.14320.4815-0.0560.0114-0.1011-0.11660.09980.2523-0.0089-0.01420.1369-0.00320.148313.4976-5.870533.0619
286.78360.469-0.86364.826-2.69741.77290.28690.28070.00280.5193-0.245-0.7088-0.08830.68970.05070.2012-0.039-0.02680.26420.01570.302325.43712.568327.8299
296.3998-0.66860.31773.02834.60717.3437-0.08330.20670.3427-0.8056-0.08040.066-0.28210.16890.16820.1744-0.01060.00540.20130.01180.209915.44581.405120.2187
300.51641.30990.25414.03662.17043.6019-0.0653-0.16280.1555-0.1196-0.19150.4141-0.5754-0.57180.18420.2860.0264-0.00140.243-0.02490.260210.6845.533525.1616
317.2292-0.10243.71665.6738-0.38651.94510.4613-0.83310.32411.3739-0.68680.5759-0.7016-0.44610.2730.7102-0.1259-0.02570.3252-0.03530.281116.8172-0.364542.5957
327.77880.90241.027.4599-3.49362.02110.2101-1.22130.0961.26250.39490.2283-0.6916-0.394-0.57930.55150.0338-0.00190.43420.00520.349615.50255.974638.0934
330.2212-0.0799-0.21850.13420.0070.39080.3769-0.5288-0.09570.5305-0.33950.46580.372-0.9482-0.00590.5716-0.0025-0.12350.5563-0.10060.4228-7.4637-14.2378-6.8212
340.77390.54060.04210.4383-0.04860.10520.1011-0.28980.83410.6898-0.34030.2362-0.0542-0.7068-0.00450.5844-0.0533-0.03690.3759-0.02850.32729.5258-7.107942.7941
357.69381.4668-2.64064.91263.19963.8666-1.06030.02740.56520.2805-0.03880.72720.31610.49371.07830.34720.0338-0.00520.3737-0.0150.4836-4.49282.27171.0797
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND RESID 33:57 )A33 - 57
2X-RAY DIFFRACTION2( CHAIN A AND RESID 58:64 )A58 - 64
3X-RAY DIFFRACTION3( CHAIN A AND RESID 65:78 )A65 - 78
4X-RAY DIFFRACTION4( CHAIN A AND RESID 79:87 )A79 - 87
5X-RAY DIFFRACTION5( CHAIN A AND RESID 88:104 )A88 - 104
6X-RAY DIFFRACTION6( CHAIN A AND RESID 105:109 )A105 - 109
7X-RAY DIFFRACTION7( CHAIN A AND RESID 110:124 )A110 - 124
8X-RAY DIFFRACTION8( CHAIN A AND RESID 125:141 )A125 - 141
9X-RAY DIFFRACTION9( CHAIN A AND RESID 142:147 )A142 - 147
10X-RAY DIFFRACTION10( CHAIN A AND RESID 148:168 )A148 - 168
11X-RAY DIFFRACTION11( CHAIN A AND RESID 169:174 )A169 - 174
12X-RAY DIFFRACTION12( CHAIN A AND RESID 175:184 )A175 - 184
13X-RAY DIFFRACTION13( CHAIN A AND RESID 185:189 )A185 - 189
14X-RAY DIFFRACTION14( CHAIN A AND RESID 190:198 )A190 - 198
15X-RAY DIFFRACTION15( CHAIN A AND RESID 199:206 )A199 - 206
16X-RAY DIFFRACTION16( CHAIN A AND RESID 207:217 )A207 - 217
17X-RAY DIFFRACTION17( CHAIN B AND RESID 35:40 )B35 - 40
18X-RAY DIFFRACTION18( CHAIN B AND RESID 41:49 )B41 - 49
19X-RAY DIFFRACTION19( CHAIN B AND RESID 50:55 )B50 - 55
20X-RAY DIFFRACTION20( CHAIN B AND RESID 56:77 )B56 - 77
21X-RAY DIFFRACTION21( CHAIN B AND RESID 78:82 )B78 - 82
22X-RAY DIFFRACTION22( CHAIN B AND RESID 83:102 )B83 - 102
23X-RAY DIFFRACTION23( CHAIN B AND RESID 103:107 )B103 - 107
24X-RAY DIFFRACTION24( CHAIN B AND RESID 108:125 )B108 - 125
25X-RAY DIFFRACTION25( CHAIN B AND RESID 126:142 )B126 - 142
26X-RAY DIFFRACTION26( CHAIN B AND RESID 143:147 )B143 - 147
27X-RAY DIFFRACTION27( CHAIN B AND RESID 148:170 )B148 - 170
28X-RAY DIFFRACTION28( CHAIN B AND RESID 171:180 )B171 - 180
29X-RAY DIFFRACTION29( CHAIN B AND RESID 181:186 )B181 - 186
30X-RAY DIFFRACTION30( CHAIN B AND RESID 187:197 )B187 - 197
31X-RAY DIFFRACTION31( CHAIN B AND RESID 198:206 )B198 - 206
32X-RAY DIFFRACTION32( CHAIN B AND RESID 207:217 )B207 - 217
33X-RAY DIFFRACTION33( CHAIN A AND RESID 301:301 )A301
34X-RAY DIFFRACTION34( CHAIN B AND RESID 301:301 )B301
35X-RAY DIFFRACTION35( CHAIN A AND RESID 302:302 )A302

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