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- PDB-6c6z: Crystal structure of potent neutralizing antibody CDC2-C2 in comp... -

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Basic information

Entry
Database: PDB / ID: 6c6z
TitleCrystal structure of potent neutralizing antibody CDC2-C2 in complex with MERS-CoV S1 RBD
Components
  • Antibody CDC2-C2 heavy chain
  • Antibody CDC2-C2 light chain
  • Spike protein
KeywordsIMMUNE SYSTEM / antibody / fusion glycoprotein / virus / ANTIVIRAL PROTEIN
Function / homology
Function and homology information


endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
ubp-family deubiquitinating enzyme fold - #30 / Spike protein, C-terminal core receptor binding subdomain / ubp-family deubiquitinating enzyme fold / Spike (S) protein S1 subunit, receptor-binding domain, MERS-CoV / Spike (S) protein S1 subunit, N-terminal domain, MERS-CoV-like / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion / Single Sheet / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily ...ubp-family deubiquitinating enzyme fold - #30 / Spike protein, C-terminal core receptor binding subdomain / ubp-family deubiquitinating enzyme fold / Spike (S) protein S1 subunit, receptor-binding domain, MERS-CoV / Spike (S) protein S1 subunit, N-terminal domain, MERS-CoV-like / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion / Single Sheet / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Alpha-Beta Plaits / Immunoglobulins / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Spike glycoprotein / Spike glycoprotein
Similarity search - Component
Biological speciesMiddle East respiratory syndrome-related coronavirus
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsWang, N. / McLellan, J.S.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI127521 United States
CitationJournal: J. Virol. / Year: 2018
Title: Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape.
Authors: Wang, L. / Shi, W. / Chappell, J.D. / Joyce, M.G. / Zhang, Y. / Kanekiyo, M. / Becker, M.M. / van Doremalen, N. / Fischer, R. / Wang, N. / Corbett, K.S. / Choe, M. / Mason, R.D. / Van Galen, ...Authors: Wang, L. / Shi, W. / Chappell, J.D. / Joyce, M.G. / Zhang, Y. / Kanekiyo, M. / Becker, M.M. / van Doremalen, N. / Fischer, R. / Wang, N. / Corbett, K.S. / Choe, M. / Mason, R.D. / Van Galen, J.G. / Zhou, T. / Saunders, K.O. / Tatti, K.M. / Haynes, L.M. / Kwong, P.D. / Modjarrad, K. / Kong, W.P. / McLellan, J.S. / Denison, M.R. / Munster, V.J. / Mascola, J.R. / Graham, B.S.
History
DepositionJan 19, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 31, 2018Provider: repository / Type: Initial release
Revision 1.1Feb 14, 2018Group: Derived calculations
Category: pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list
Item: _pdbx_struct_assembly_prop.value
Revision 1.2Mar 21, 2018Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.3Apr 3, 2019Group: Data collection / Database references / Category: citation / Item: _citation.journal_volume / _citation.title
Revision 1.4Dec 11, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Jul 29, 2020Group: Data collection / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_conn.pdbx_role
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.6Oct 4, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _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: Spike protein
B: Spike protein
C: Antibody CDC2-C2 heavy chain
D: Antibody CDC2-C2 light chain
H: Antibody CDC2-C2 heavy chain
L: Antibody CDC2-C2 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)149,0869
Polymers148,4226
Non-polymers6643
Water12,953719
1
A: Spike protein
C: Antibody CDC2-C2 heavy chain
D: Antibody CDC2-C2 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)74,4324
Polymers74,2113
Non-polymers2211
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5260 Å2
ΔGint-24 kcal/mol
Surface area28410 Å2
MethodPISA
2
B: Spike protein
H: Antibody CDC2-C2 heavy chain
L: Antibody CDC2-C2 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)74,6545
Polymers74,2113
Non-polymers4422
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5470 Å2
ΔGint-18 kcal/mol
Surface area29030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.819, 166.850, 184.819
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Spike protein


Mass: 25337.531 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Middle East respiratory syndrome-related coronavirus
Production host: Homo sapiens (human) / References: UniProt: A0A0U2MS80, UniProt: K9N5Q8*PLUS
#2: Antibody Antibody CDC2-C2 heavy chain


Mass: 25171.232 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#3: Antibody Antibody CDC2-C2 light chain


Mass: 23702.395 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#4: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 719 / Source method: isolated from a natural source / Formula: H2O

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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: 3.16 Å3/Da / Density % sol: 61.06 %
Crystal growTemperature: 293 K / Method: liquid diffusion / pH: 6.5
Details: 0.1 M Tris, pH 6.5, 10% (vol/vol) 2-propanol, and 10% (wt/wt) PEG 3350

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.9792 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 9, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.1→47.652 Å / Num. obs: 107760 / % possible obs: 97.7 % / Redundancy: 6.3 % / Biso Wilson estimate: 33.11 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.128 / Rpim(I) all: 0.054 / Rrim(I) all: 0.14 / Net I/σ(I): 8.3
Reflection shell

Diffraction-ID: 1 / Redundancy: 6.4 %

Resolution (Å)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible all
2.1-2.141.22352020.6950.511.33197.3
11.5-47.650.0677860.9950.030.07398.1

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Processing

Software
NameVersionClassification
PHENIX1.12_2829refinement
Aimless0.5.31data scaling
PDB_EXTRACT3.22data extraction
iMOSFLMdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4XAK
Resolution: 2.1→47.652 Å / SU ML: 0.24 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.35
RfactorNum. reflection% reflection
Rfree0.2279 5384 5 %
Rwork0.1907 --
obs0.1925 107581 97.27 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 124.33 Å2 / Biso mean: 42.8555 Å2 / Biso min: 17.54 Å2
Refinement stepCycle: final / Resolution: 2.1→47.652 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9519 0 42 719 10280
Biso mean--74.87 46.28 -
Num. residues----1251
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0059804
X-RAY DIFFRACTIONf_angle_d0.72813350
X-RAY DIFFRACTIONf_chiral_restr0.051509
X-RAY DIFFRACTIONf_plane_restr0.0051699
X-RAY DIFFRACTIONf_dihedral_angle_d11.6445858
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.1-2.12390.32471780.25933309348797
2.1239-2.14890.30491760.25693354353097
2.1489-2.17510.31172030.25033313351696
2.1751-2.20260.30221770.24563342351997
2.2026-2.23160.28151480.24153366351496
2.2316-2.26210.29451970.23883334353196
2.2621-2.29450.26791600.22213179333993
2.2945-2.32870.25731900.223332352295
2.3287-2.36510.27921950.21563385358099
2.3651-2.40390.23032090.21313412362199
2.4039-2.44530.28261700.21423454362499
2.4453-2.48980.26571720.20163423359599
2.4898-2.53770.23951660.20323451361798
2.5377-2.58950.26011910.19873349354098
2.5895-2.64580.25431840.2033430361498
2.6458-2.70730.25151890.21033370355998
2.7073-2.7750.27551820.20693369355196
2.775-2.850.2361780.20613267344595
2.85-2.93390.2341730.20723468364199
2.9339-3.02860.22991720.20873487365999
3.0286-3.13680.2521920.20573443363599
3.1368-3.26230.24181880.19563429361798
3.2623-3.41080.2471650.19573465363097
3.4108-3.59050.24321640.19233441360597
3.5905-3.81540.19691790.17793382356196
3.8154-4.10990.21141690.173510367999
4.1099-4.52320.16291790.14233516369599
4.5232-5.1770.1562070.1383443365097
5.177-6.51980.2031700.17153506367696
6.5198-47.66420.22141610.19663668382996
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)
14.17670.9288-0.3464.1318-1.09520.7332-0.18880.39980.0827-0.85670.0764-0.48690.2260.21650.09530.4102-0.07950.05610.2773-0.00950.31650.6504-11.4167-3.1875
27.74092.0648-2.01733.8234-1.6741.763-0.12991.56670.5336-0.55920.5824-0.4026-0.47850.0692-0.36060.497-0.09280.04530.50450.05240.3674-5.4974-6.6466-12.3913
37.0140.25272.01037.37980.54323.68740.03390.4030.4042-0.6007-0.0408-0.0675-0.19980.1573-0.02770.3417-0.0080.02940.2377-0.00430.2443-6.7397-4.3469-2.6672
46.1149-1.42172.09447.55033.22492.7447-0.1775-0.47251.1820.595-0.0393-0.4459-0.7725-0.78780.26510.47080.0354-0.01490.3205-0.0360.4342-12.3695-5.649910.2331
51.0647-1.4682.27842.1597-3.14524.8399-0.17630.01070.51910.3475-0.4409-0.3203-1.18810.54250.5070.526-0.089-0.08430.2537-0.01260.4877-3.53250.60458.7584
62.06891.4751.80361.40141.43063.48030.2359-0.20370.03780.2705-0.1908-0.13380.3556-0.261-0.03640.2677-0.01650.01660.2101-0.02230.2888-2.9484-11.025212.341
72.4913-0.39842.16650.22480.29914.3385-0.040.04210.19430.00160.0178-0.1076-0.13790.24040.03440.2783-0.08020.0190.207-0.04220.28081.45-10.328813.9052
85.01831.4052.20583.2120.68730.9955-0.3430.65550.1732-1.30710.39870.09170.3766-0.5663-0.04380.7173-0.1537-0.03340.35780.07740.4267-31.759714.4722-7.8299
93.04810.3364-0.21753.1099-1.1450.4343-0.00740.6827-0.174-0.45540.02060.29870.2997-0.6205-0.01110.3-0.07-0.02650.357-0.07480.3463-29.69958.3522-6.7093
104.5785-0.4417-1.53827.3807-0.3934.03140.02710.3503-0.371-0.4934-0.14680.09120.3852-0.21230.09610.29-0.02380.01320.2436-0.03630.293-25.30825.444-2.7965
115.16294.6664-5.0164.1844-4.49474.8961-0.2198-0.6009-0.7324-0.1593-0.104-0.55940.60230.63890.44370.37540.0073-0.01020.3349-0.02040.4456-21.59936.354211.3621
122.90280.1644-1.05771.36131.79624.5086-0.03480.1374-0.68610.4154-0.27270.03780.7427-0.22960.28540.2979-0.05670.01140.2008-0.02040.3877-25.95791.65492.7102
133.14841.6056-3.12561.1492-2.176.26280.0320.0045-0.01070.0141-0.04180.01980.0761-0.15890.01450.3103-0.0332-0.00890.1727-0.04220.3289-32.384910.729614.0589
143.3444-0.4048-2.97860.2639-0.20344.64480.2694-0.01060.10990.062-0.0442-0.0608-0.3222-0.0604-0.20520.2223-0.0675-0.01310.1964-0.0080.2852-32.853913.184614.1473
153.08290.3727-1.84892.9731-0.45176.1449-0.0815-0.25640.05580.28770.0578-0.0071-0.09330.1292-0.02810.24740.01910.00620.1925-0.02430.2195-1.9277-17.129846.7395
163.76933.6005-4.32493.5547-4.13756.4799-0.04580.70130.2869-0.05550.37650.3597-0.2743-0.7364-0.34210.28530.0196-0.00760.4413-0.01010.3737-9.1243-14.326938.8026
170.450.565-0.33190.7594-1.60536.02050.0345-0.03610.04940.07670.0799-0.01930.1058-0.0855-0.1160.28080.01390.01490.2111-0.04290.2796-3.0398-22.666154.2845
185.5367-0.81430.84574.2947-0.51826.14020.1479-0.1173-0.01970.2948-0.029-0.64220.43780.4045-0.07660.36760.03420.0220.2507-0.03020.30891.2201-31.410976.1069
191.9361-0.03030.7083.3993-3.38218.2547-0.1046-0.1628-0.3508-0.11160.16850.0850.7804-0.2555-0.04350.4273-0.01040.080.2653-0.05090.3247-0.699-39.852435.5458
200.8740.2712-0.36823.7571-1.66325.158-0.2172-0.1196-0.26830.06950.0624-0.42270.44740.46530.15010.35470.0750.07080.2687-0.02770.30644.9575-37.464842.2278
214.5641-1.1233-2.92562.87351.18053.43470.09070.0132-0.05190.6394-0.2235-0.08140.8013-0.38160.0630.7782-0.12510.00250.3677-0.00020.339-9.793-44.214774.2557
223.3517-0.3111-2.74654.06610.35795.10560.1328-0.206-0.40080.5531-0.35710.22411.0054-0.25180.22710.763-0.1589-0.03950.4411-0.03870.3143-9.5103-45.700572.3585
231.88980.07481.42492.83641.17465.4977-0.00350.1061-0.17320.06140.08540.0170.26760.0689-0.08170.1912-0.03170.02420.1763-0.00120.2192-28.099517.179844.0011
243.8241-2.3596-1.864.97781.73744.99070.129-0.1408-0.01480.25170.01550.2539-0.0432-0.0569-0.14260.2174-0.0373-0.04230.22050.03730.2266-28.332930.866277.064
251.1491-0.513-0.11374.38571.24177.34560.00290.08960.1242-0.436-0.070.0669-0.3066-0.0630.05950.23280.0137-0.0520.25890.04030.2559-35.158237.599138.5474
261.08030.17831.250.9810.01613.8144-0.0539-0.07710.0155-0.0197-0.01240.0183-0.239-0.27710.05240.2111-0.01540.00460.18140.04440.2384-29.633839.189257.9536
276.4467-1.00132.65791.6936-0.74031.3231-0.00480.15530.12110.0058-0.0863-0.0874-0.24330.18810.10420.3742-0.0049-0.0130.2603-0.00890.2229-18.512544.667969.2784
287.798-1.98686.34933.5153-2.15337.18560.0816-0.03850.15120.3517-0.2154-0.1864-0.45010.19820.12370.2857-0.04730.07020.239-0.00270.1682-19.966245.478373.2388
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 381 through 404 )A381 - 404
2X-RAY DIFFRACTION2chain 'A' and (resid 405 through 418 )A405 - 418
3X-RAY DIFFRACTION3chain 'A' and (resid 419 through 447 )A419 - 447
4X-RAY DIFFRACTION4chain 'A' and (resid 448 through 462 )A448 - 462
5X-RAY DIFFRACTION5chain 'A' and (resid 463 through 476 )A463 - 476
6X-RAY DIFFRACTION6chain 'A' and (resid 477 through 515 )A477 - 515
7X-RAY DIFFRACTION7chain 'A' and (resid 516 through 578 )A516 - 578
8X-RAY DIFFRACTION8chain 'B' and (resid 380 through 395 )B380 - 395
9X-RAY DIFFRACTION9chain 'B' and (resid 396 through 418 )B396 - 418
10X-RAY DIFFRACTION10chain 'B' and (resid 419 through 447 )B419 - 447
11X-RAY DIFFRACTION11chain 'B' and (resid 448 through 467 )B448 - 467
12X-RAY DIFFRACTION12chain 'B' and (resid 468 through 483 )B468 - 483
13X-RAY DIFFRACTION13chain 'B' and (resid 484 through 528 )B484 - 528
14X-RAY DIFFRACTION14chain 'B' and (resid 529 through 578 )B529 - 578
15X-RAY DIFFRACTION15chain 'C' and (resid 1 through 52 )C1 - 52
16X-RAY DIFFRACTION16chain 'C' and (resid 53 through 72 )C53 - 72
17X-RAY DIFFRACTION17chain 'C' and (resid 73 through 145 )C73 - 145
18X-RAY DIFFRACTION18chain 'C' and (resid 146 through 214 )C146 - 214
19X-RAY DIFFRACTION19chain 'D' and (resid 2 through 32 )D2 - 32
20X-RAY DIFFRACTION20chain 'D' and (resid 33 through 113 )D33 - 113
21X-RAY DIFFRACTION21chain 'D' and (resid 114 through 155 )D114 - 155
22X-RAY DIFFRACTION22chain 'D' and (resid 156 through 212 )D156 - 212
23X-RAY DIFFRACTION23chain 'H' and (resid 1 through 111 )H1 - 111
24X-RAY DIFFRACTION24chain 'H' and (resid 112 through 214 )H112 - 214
25X-RAY DIFFRACTION25chain 'L' and (resid 2 through 75 )L2 - 75
26X-RAY DIFFRACTION26chain 'L' and (resid 76 through 128 )L76 - 128
27X-RAY DIFFRACTION27chain 'L' and (resid 129 through 163 )L129 - 163
28X-RAY DIFFRACTION28chain 'L' and (resid 164 through 212 )L164 - 212

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