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- PDB-9atm: SARS-CoV-2 EG.5 RBD bound to the VIR-7229 and the S2H97 Fab fragments -

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Open data


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Basic information

Entry
Database: PDB / ID: 9atm
TitleSARS-CoV-2 EG.5 RBD bound to the VIR-7229 and the S2H97 Fab fragments
Components
  • (VIR-7229 Fab ...) x 2
  • S2H97 Fab heavy chain
  • S2H97 Fab light chain
  • SARS-CoV-2 EG.5 RBD
KeywordsVIRAL PROTEIN / Sarbecoviruses / Spike glycoprotein / fusion protein / neutralizing antibodies / inhibitor / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID
Function / homologyNICKEL (II) ION
Function and homology information
Biological speciesHomo sapiens (human)
Severe acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsRietz, T. / Park, Y.J. / Errico, J. / Czudnochowski, N. / Nix, J.C. / Corti, D. / Snell, G. / Marco, A.D. / Pinto, D. / Cameroni, E. ...Rietz, T. / Park, Y.J. / Errico, J. / Czudnochowski, N. / Nix, J.C. / Corti, D. / Snell, G. / Marco, A.D. / Pinto, D. / Cameroni, E. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler, D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)75N93022C00036 United States
CitationJournal: Cell / Year: 2024
Title: A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.
Authors: Laura E Rosen / M Alejandra Tortorici / Anna De Marco / Dora Pinto / William B Foreman / Ashley L Taylor / Young-Jun Park / Dana Bohan / Tyson Rietz / John M Errico / Kevin Hauser / Ha V ...Authors: Laura E Rosen / M Alejandra Tortorici / Anna De Marco / Dora Pinto / William B Foreman / Ashley L Taylor / Young-Jun Park / Dana Bohan / Tyson Rietz / John M Errico / Kevin Hauser / Ha V Dang / Justin W Chartron / Martina Giurdanella / Giuseppe Cusumano / Christian Saliba / Fabrizia Zatta / Kaitlin R Sprouse / Amin Addetia / Samantha K Zepeda / Jack Brown / Jimin Lee / Exequiel Dellota / Anushka Rajesh / Julia Noack / Qiqing Tao / Yvonne DaCosta / Brian Tsu / Rima Acosta / Sambhavi Subramanian / Guilherme Dias de Melo / Lauriane Kergoat / Ivy Zhang / Zhuoming Liu / Barbara Guarino / Michael A Schmid / Gretja Schnell / Jessica L Miller / Florian A Lempp / Nadine Czudnochowski / Elisabetta Cameroni / Sean P J Whelan / Hervé Bourhy / Lisa A Purcell / Fabio Benigni / Julia di Iulio / Matteo Samuele Pizzuto / Antonio Lanzavecchia / Amalio Telenti / Gyorgy Snell / Davide Corti / David Veesler / Tyler N Starr /
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.
History
DepositionFeb 27, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 2.0Oct 23, 2024Group: Atomic model / Data collection / Derived calculations
Category: atom_site / pdbx_nonpoly_scheme ...atom_site / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _pdbx_nonpoly_scheme.auth_seq_num / _pdbx_struct_assembly_prop.value
Revision 2.1Dec 25, 2024Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: VIR-7229 Fab heavy chain
I: S2H97 Fab heavy chain
L: VIR-7229 Fab light chain
M: S2H97 Fab light chain
R: SARS-CoV-2 EG.5 RBD
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,03712
Polymers121,4135
Non-polymers6247
Water12,178676
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area11720 Å2
ΔGint-70 kcal/mol
Surface area45830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.728, 149.698, 167.078
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "L" and (resid 2 through 7 or resid 9...
d_2ens_1(chain "M" and (resid 2 through 7 or resid 9...

NCS domain segments:

Ens-ID: ens_1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11SERSERPROPROLC2 - 72 - 7
d_12SERSERSERSERLC9 - 179 - 17
d_13THRTHRGLYGLYLC19 - 2419 - 24
d_14SERSERGLYGLYLC26 - 3026 - 30
d_15TYRTYRASNASNLC32 - 3332 - 33
d_16VALVALLYSLYSLC35 - 4735 - 47
d_17METMETVALVALLC49 - 5349 - 53
d_18ARGARGVALVALLC56 - 6056 - 60
d_19ARGARGLEULEULC63 - 7563 - 75
d_110ILEILETYRTYRLC77 - 9377 - 93
d_111SERSERSERSERLC9696
d_112VALVALGLYGLYLC100 - 102100 - 102
d_113GLYGLYTHRTHRLC104 - 105104 - 105
d_114VALVALGLUGLULC109 - 214109 - 214
d_21SERSERPROPROMD2 - 72 - 7
d_22SERSERSERSERMD9 - 179 - 17
d_23THRTHRGLYGLYMD19 - 2419 - 24
d_24SERSERGLYGLYMD26 - 3026 - 30
d_25TYRTYRASNASNMD32 - 3332 - 33
d_26VALVALLYSLYSMD35 - 4735 - 47
d_27METMETVALVALMD49 - 5349 - 53
d_28ARGARGVALVALMD56 - 6056 - 60
d_29ARGARGLEULEUMD63 - 7563 - 75
d_210ILEILETYRTYRMD77 - 9377 - 93
d_211SERSERSERSERMD9696
d_212VALVALGLYGLYMD102 - 104102 - 104
d_213GLYGLYTHRTHRMD106 - 107106 - 107
d_214VALVALGLUGLUMD111 - 216111 - 216

NCS oper: (Code: givenMatrix: (0.392452501459, -0.889420877472, -0.234332107949), (-0.908321095319, -0.334700206916, -0.25085565429), (0.14468525114, 0.311297725991, -0.939233679068)Vector: -5. ...NCS oper: (Code: given
Matrix: (0.392452501459, -0.889420877472, -0.234332107949), (-0.908321095319, -0.334700206916, -0.25085565429), (0.14468525114, 0.311297725991, -0.939233679068)
Vector: -5.58137826198, 12.0256893114, -31.6038046509)

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Components

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Antibody , 4 types, 4 molecules HILM

#1: Antibody VIR-7229 Fab heavy chain


Mass: 24259.188 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#2: Antibody S2H97 Fab heavy chain


Mass: 24157.113 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#3: Antibody VIR-7229 Fab light chain


Mass: 22993.303 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#4: Antibody S2H97 Fab light chain


Mass: 22935.219 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

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Protein / Sugars , 2 types, 2 molecules R

#10: 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.: 1 / Source method: obtained synthetically / 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: Protein SARS-CoV-2 EG.5 RBD


Mass: 27068.621 Da / Num. of mol.: 1 / Fragment: RBD
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Strain: EG.5 / Production host: Homo sapiens (human)

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Non-polymers , 5 types, 682 molecules

#6: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#7: Chemical ChemComp-NI / NICKEL (II) ION


Mass: 58.693 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ni
#8: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: Cl
#9: Chemical ChemComp-TRS / 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / TRIS BUFFER


Mass: 122.143 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H12NO3 / Comment: pH buffer*YM
#11: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 676 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN
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: 2.51 Å3/Da / Density % sol: 50.99 %
Crystal growTemperature: 293 K / Method: vapor diffusion
Details: 0.1 M TRIS pH 8, 22% w/v PEG-MME 2000, and 20 mM NiCl2

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Data collection

DiffractionMean temperature: 293 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 14-BM-C / Wavelength: 1.195 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 6, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.195 Å / Relative weight: 1
ReflectionResolution: 1.9→46.78 Å / Num. obs: 92795 / % possible obs: 99.91 % / Redundancy: 13.1 % / Biso Wilson estimate: 36.44 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.138 / Net I/σ(I): 12.8
Reflection shellResolution: 1.9→1.92 Å / Mean I/σ(I) obs: 0.6 / Num. unique obs: 3168 / CC1/2: 0.323

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Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
PHASER2.8.3phasing
XDSJune 30, 2023data reduction
Aimless0.7.4data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→46.78 Å / SU ML: 0.2789 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.0051
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2272 4870 5.01 %
Rwork0.1939 92425 -
obs0.1956 97295 99.91 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 53.96 Å2
Refinement stepCycle: LAST / Resolution: 1.9→46.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7948 0 36 676 8660
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00658232
X-RAY DIFFRACTIONf_angle_d0.845411262
X-RAY DIFFRACTIONf_chiral_restr0.05681259
X-RAY DIFFRACTIONf_plane_restr0.00591439
X-RAY DIFFRACTIONf_dihedral_angle_d14.39952840
Refine LS restraints NCSType: Torsion NCS / Rms dev position: 4.29210732005 Å
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9-1.920.42761510.40123017X-RAY DIFFRACTION99.69
1.92-1.940.38471480.3693101X-RAY DIFFRACTION99.94
1.94-1.970.36031540.35283024X-RAY DIFFRACTION99.94
1.97-1.990.30991950.32492983X-RAY DIFFRACTION100
1.99-2.020.37871510.32083092X-RAY DIFFRACTION100
2.02-2.050.29521600.29583017X-RAY DIFFRACTION100
2.05-2.080.30161630.28863034X-RAY DIFFRACTION99.97
2.08-2.110.27251410.27093096X-RAY DIFFRACTION99.97
2.11-2.140.30771680.27383009X-RAY DIFFRACTION99.84
2.14-2.170.29091570.25183061X-RAY DIFFRACTION100
2.17-2.210.29781690.25453061X-RAY DIFFRACTION99.85
2.21-2.250.31511650.2423028X-RAY DIFFRACTION99.91
2.25-2.30.2791790.23563035X-RAY DIFFRACTION100
2.3-2.340.25681560.22513067X-RAY DIFFRACTION99.97
2.34-2.390.31841230.21763080X-RAY DIFFRACTION99.91
2.39-2.450.26441600.20853093X-RAY DIFFRACTION99.94
2.45-2.510.25121650.19943026X-RAY DIFFRACTION100
2.51-2.580.22181660.19653120X-RAY DIFFRACTION99.97
2.58-2.650.24931680.19342999X-RAY DIFFRACTION99.75
2.65-2.740.23711710.19053089X-RAY DIFFRACTION99.94
2.74-2.840.23411580.19193092X-RAY DIFFRACTION99.94
2.84-2.950.23271560.20883079X-RAY DIFFRACTION100
2.95-3.090.28531560.23102X-RAY DIFFRACTION99.94
3.09-3.250.24221750.19513103X-RAY DIFFRACTION100
3.25-3.450.21911600.18143099X-RAY DIFFRACTION99.88
3.45-3.720.21871720.18243123X-RAY DIFFRACTION99.97
3.72-4.090.19661800.16083108X-RAY DIFFRACTION100
4.09-4.680.17241630.13593143X-RAY DIFFRACTION99.64
4.68-5.90.17271660.14983172X-RAY DIFFRACTION99.58
5.9-46.780.18251740.18133372X-RAY DIFFRACTION99.86
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)
12.35727447719-0.7232950199361.686724996151.81399550782-0.6621713635213.330779272310.03911330574010.10058495961-0.0298085962889-0.084802380922-0.0546567736544-0.167136693191-0.05653098068230.2560221522470.0154701889850.282289577740.0005408610623740.007622701484830.2753943564020.01444580028450.26149413969930.8013072836-23.6919090841-0.163762433269
23.267468466850.572346919431-0.1601402583114.54081796459-2.009221884048.573240716280.028054837872-0.229030280358-0.04410628358030.569435258246-0.123297657590.2254438299420.181906510752-0.2227107662250.06997602057010.329704610443-0.0443236066266-0.01137979668930.244807427377-0.0254017627640.29069508849342.4631810614-37.12838067132.8419014101
32.10977084074-0.812798567984-0.1103521306542.765755268650.3456904608882.555686296490.1463189468930.1547612397730.0812235483483-0.215044643947-0.0612450798614-0.4723024899290.253565711620.375686884503-0.08938750106470.2722051661970.05880694981560.04411410922360.3591992756770.07693892108550.36232543867926.8222316859-11.4378406982-35.0396273772
48.22746933317-1.651367290742.667444113273.23942976725-1.675602792842.25957105502-0.4983905990530.242785987885-0.472212150324-0.0424910327630.32905859442-0.05738635005980.7016541807241.415361896440.1364177772620.9069640301650.4122484439780.2099819480011.140098486390.01962932075880.75982774266536.3923172968-23.2936068615-73.3787035628
53.26010732788-0.2882366437470.1877577162413.00931356621-0.3945687012844.71278076310.0161983937936-0.4719474316220.1078575451010.05688410916710.01646389035280.170394536896-0.312216398113-0.477002383325-0.0447485053850.3480624683970.0934652731315-0.004531167035180.40648615047-0.03835041033880.25067951974317.5147658778-13.688110434913.1083031897
69.20040957445-1.622341733360.8813279982723.02055727518-0.4027165734525.056146803190.00723879977405-0.1972097984390.142828915010.2689214377690.0915952432461-0.0519285334914-0.0519783345709-0.35251091143-0.1099248419650.429916769681-0.0499133636008-0.07765122577720.308168845006-0.006542155090340.26569523236440.0220182383-22.640882944538.6576751247
70.8020645570030.0123896769377-0.5997685757111.073290872120.1332235454925.884117586270.09172751410580.217846157772-0.0651088866763-0.264643636106-0.131083035665-0.0301301647154-0.0471356078529-0.2543777857640.0307474221390.338080524270.09966376327280.02005288949780.4215655584860.08614083531230.34573093105811.0913295053-5.82171838719-49.3307305697
82.33517117479-1.533258208941.799756350312.6723909122-0.8652689814752.3542017264-0.473749387783-0.286091960528-1.522819260160.1405067992220.30781328698-0.02979240351350.99451587480.4549754397590.05242149149361.087245384620.2695040297240.3873464451210.6673866139180.1797119361561.2349547262720.7803190229-25.1379072988-67.3301037919
93.41415968679-1.164219520121.284312720554.58555339593-3.349163386423.827787118720.3457856250080.008564960471840.19508355801-0.4382507327740.20973554491.06629778477-0.359102826928-0.73516480203-0.5417176617460.4294539610430.1622767023730.0260196703870.4594337220480.05452263958330.485184179887-2.44606692973.92782732064-17.6474323902
102.16146277686-0.56676491131.338644464541.73068134774-0.3687590917574.8063766437-0.0732876350233-0.3282512748010.6672786341340.4211118505120.1008569806710.0402537702588-1.3880115382-0.716514987899-0.03418491770480.7268896189930.1734016889470.06128359905210.4499701048460.01413109183650.6008995059875.0692626085512.9455980812-18.5540134195
112.89872681916-0.545403593392-0.4044656502322.113676336160.1470337199471.732738329160.0207130167901-0.17872764706-0.1470001593410.1191613150210.06001100377040.1439022405210.0988512891432-0.120938918335-0.09055496368470.2938624544680.0343545421682-0.05324439274610.2735286595420.01132325595910.2472034363977.682209578-9.07266829735-10.6580506281
123.52872322280.945610234118-3.290801507810.9867255018550.3948191261254.916102421050.0579696125648-0.4533322362060.03487775479860.31932664367-0.133963501534-0.065140150711-0.04337288777140.221040703540.1276933720920.4168372247390.1113405749080.005892305010020.3992140478550.01725453765970.3381489962963.073083264830.197508674006-4.43531060099
132.59754121186-2.345024532870.3035254968132.75103690732-1.022751677090.9772230397031.055337376750.3557765812471.02246812308-0.347746497682-0.149976429319-0.276751882031-1.23755394509-0.46652913274-0.7962624275070.7352680921710.1419640709690.1909187776980.3643039519120.1464758551390.5827236284938.9230858854314.4209636712-31.5537147628
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'H' and (resid 1 through 123 )HA1 - 1231 - 125
22chain 'H' and (resid 124 through 226 )HA124 - 226126 - 227
33chain 'I' and (resid 2 through 118 )IB2 - 1182 - 121
44chain 'I' and (resid 119 through 220 )IB119 - 220122 - 217
55chain 'L' and (resid 2 through 110 )LC2 - 1102 - 110
66chain 'L' and (resid 111 through 215 )LC111 - 215111 - 215
77chain 'M' and (resid 1 through 124 )MD1 - 1241 - 124
88chain 'M' and (resid 125 through 216 )MD125 - 216125 - 216
99chain 'R' and (resid 333 through 353 )RF333 - 3531 - 21
1010chain 'R' and (resid 354 through 393 )RF354 - 39322 - 61
1111chain 'R' and (resid 394 through 494 )RF394 - 49462 - 164
1212chain 'R' and (resid 495 through 516 )RF495 - 516165 - 188
1313chain 'R' and (resid 517 through 529 )RF517 - 529189 - 201

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