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- PDB-2vxs: Structure of IL-17A in complex with a potent, fully human neutral... -

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Basic information

Entry
Database: PDB / ID: 2vxs
TitleStructure of IL-17A in complex with a potent, fully human neutralising antibody
Components
  • (FAB FRAGMENT) x 2
  • INTERLEUKIN-17A
KeywordsCYTOKINE / EPITOPE / COMPLEX / ANTIBODY / SECRETED / GLYCOPROTEIN / INTERLEUKIN-17
Function / homology
Function and homology information


positive regulation of interleukin-16 production / granulocyte migration / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / intestinal epithelial structure maintenance / negative regulation of inflammatory response to wounding / interleukin-17A-mediated signaling pathway / positive regulation of interleukin-23 production / cell death / positive regulation of chemokine (C-X-C motif) ligand 1 production ...positive regulation of interleukin-16 production / granulocyte migration / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / intestinal epithelial structure maintenance / negative regulation of inflammatory response to wounding / interleukin-17A-mediated signaling pathway / positive regulation of interleukin-23 production / cell death / positive regulation of chemokine (C-X-C motif) ligand 1 production / interleukin-17-mediated signaling pathway / positive regulation of bicellular tight junction assembly / fibroblast activation / positive regulation of osteoclast differentiation / positive regulation of cytokine production involved in inflammatory response / keratinocyte proliferation / cellular response to interleukin-1 / defense response to fungus / keratinocyte differentiation / Notch signaling pathway / positive regulation of interleukin-12 production / positive regulation of interleukin-1 beta production / cytokine activity / response to wounding / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / cell-cell signaling / gene expression / Interleukin-4 and Interleukin-13 signaling / defense response to Gram-negative bacterium / adaptive immune response / defense response to Gram-positive bacterium / inflammatory response / immune response / protein heterodimerization activity / external side of plasma membrane / innate immune response / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region
Similarity search - Function
Interleukin-17, chordata / Interleukin-17 family / Interleukin-17 / Cystine Knot Cytokines, subunit B / Cystine-knot cytokines / Cystine-knot cytokine / Ribbon / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.63 Å
AuthorsGerhardt, S. / Hargreaves, D. / Pauptit, R.A. / Davies, R.A. / Russell, C. / Welsh, F. / Tuske, S.J. / Coales, S.J. / Hamuro, Y. / Needham, M.R.C. ...Gerhardt, S. / Hargreaves, D. / Pauptit, R.A. / Davies, R.A. / Russell, C. / Welsh, F. / Tuske, S.J. / Coales, S.J. / Hamuro, Y. / Needham, M.R.C. / Langham, C. / Barker, W. / Bell, P. / Aziz, A. / Smith, M.J. / Dawson, S. / Abbott, W.M.
CitationJournal: J.Mol.Biol. / Year: 2009
Title: Structure of Il-17A in Complex with a Potent, Fully Human Neutralising Antibody.
Authors: Gerhardt, S. / Abbott, W.M. / Hargreaves, D. / Pauptit, R.A. / Davies, R.A. / Needham, M.R. / Langham, C. / Barker, W. / Aziz, A. / Snow, M.J. / Dawson, S. / Welsh, F. / Wilkinson, T. / ...Authors: Gerhardt, S. / Abbott, W.M. / Hargreaves, D. / Pauptit, R.A. / Davies, R.A. / Needham, M.R. / Langham, C. / Barker, W. / Aziz, A. / Snow, M.J. / Dawson, S. / Welsh, F. / Wilkinson, T. / Vaugan, T. / Beste, G. / Bishop, S. / Popovic, B. / Rees, G. / Sleeman, M. / Tuske, S.J. / Coales, S.J. / Hamuro, Y. / Russell, C.
History
DepositionJul 9, 2008Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 14, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 700 SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN ... SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW, TWO SHEETS ARE DEFINED.

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: INTERLEUKIN-17A
B: INTERLEUKIN-17A
C: INTERLEUKIN-17A
D: INTERLEUKIN-17A
H: FAB FRAGMENT
I: FAB FRAGMENT
J: FAB FRAGMENT
K: FAB FRAGMENT
L: FAB FRAGMENT
M: FAB FRAGMENT
N: FAB FRAGMENT
O: FAB FRAGMENT
hetero molecules


Theoretical massNumber of molelcules
Total (without water)251,38524
Polymers250,23212
Non-polymers1,15312
Water3,855214
1
C: INTERLEUKIN-17A
D: INTERLEUKIN-17A
J: FAB FRAGMENT
K: FAB FRAGMENT
N: FAB FRAGMENT
O: FAB FRAGMENT
hetero molecules


Theoretical massNumber of molelcules
Total (without water)125,50010
Polymers125,1166
Non-polymers3844
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area14020 Å2
ΔGint-118.6 kcal/mol
Surface area54580 Å2
MethodPQS
2
A: INTERLEUKIN-17A
B: INTERLEUKIN-17A
H: FAB FRAGMENT
I: FAB FRAGMENT
L: FAB FRAGMENT
M: FAB FRAGMENT
hetero molecules


Theoretical massNumber of molelcules
Total (without water)125,88414
Polymers125,1166
Non-polymers7698
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area15220 Å2
ΔGint-101 kcal/mol
Surface area56350 Å2
MethodPQS
Unit cell
Length a, b, c (Å)98.473, 66.708, 203.790
Angle α, β, γ (deg.)90.00, 91.65, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11H
21I
31J
41K
12L
22M
32N
42O
13A
23B
33C
43D

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1115H1 - 213
2115I1 - 213
3115J1 - 213
4115K1 - 213
1125L1 - 210
3125N1 - 210
2125M1 - 210
4125O1 - 210
1135A1 - 128
2135B1 - 128
3135C1 - 128
4135D1 - 128

NCS ensembles :
ID
1
2
3

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Components

#1: Protein
INTERLEUKIN-17A / IL-17A / IL-17 / CYTOTOXIC T-LYMPHOCYTE- ASSOCIATED ANTIGEN 8 / CTLA-8 / INTERLEUKINE-17A


Mass: 15689.864 Da / Num. of mol.: 4 / Fragment: RESIDUES 20-155
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PT7 / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: Q16552
#2: Antibody
FAB FRAGMENT


Mass: 23671.508 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli)
#3: Antibody
FAB FRAGMENT


Mass: 23196.564 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli)
#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 214 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsSWISSPROT ACCESSION NUMBER Q16552. THE NUMBERING OF THE FAB-FRAGMENT (CHAINS H,I,J,K AND L,M,N,O) ...SWISSPROT ACCESSION NUMBER Q16552. THE NUMBERING OF THE FAB-FRAGMENT (CHAINS H,I,J,K AND L,M,N,O) ARE ACCORDING TO THE NOMENCLATURE OF KABAT ET AL

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 2

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Sample preparation

CrystalDensity Matthews: 2.68 Å3/Da / Density % sol: 54 % / Description: NONE
Crystal growDetails: 90.9 MM PCTP BUFFER PH 4.0, 9.1 MM PCTP BUFFER PH 9.5, 100 MM AMMONIUM SULPHATE, 14% W/V PEG3350

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.9787
DetectorType: ADSC CCD / Detector: CCD / Date: Apr 30, 2007 / Details: TOROIDAL MIRROR
RadiationMonochromator: SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9787 Å / Relative weight: 1
ReflectionResolution: 2.63→102.1 Å / Num. obs: 79235 / % possible obs: 100 % / Observed criterion σ(I): 0 / Redundancy: 7 % / Rmerge(I) obs: 0.13 / Net I/σ(I): 11.7
Reflection shellResolution: 2.63→2.77 Å / Redundancy: 6.9 % / Rmerge(I) obs: 0.46 / Mean I/σ(I) obs: 3.7 / % possible all: 100

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Processing

Software
NameVersionClassification
REFMAC5.5.0036refinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1AQK
Resolution: 2.63→204.12 Å / Cor.coef. Fo:Fc: 0.914 / Cor.coef. Fo:Fc free: 0.868 / SU B: 24.577 / SU ML: 0.236 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.635 / ESU R Free: 0.323 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.U VALUES RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.264 3976 5 %RANDOM
Rwork0.213 ---
obs0.215 75243 99.9 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 19.75 Å2
Baniso -1Baniso -2Baniso -3
1-1.49 Å20 Å2-1.72 Å2
2---1.56 Å20 Å2
3----0.03 Å2
Refinement stepCycle: LAST / Resolution: 2.63→204.12 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15395 0 60 214 15669
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.02215829
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.3611.95621603
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.67252022
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.26324.017595
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.628152438
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.3081570
X-RAY DIFFRACTIONr_chiral_restr0.0890.22449
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.02111874
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.3551.510170
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.644216481
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it0.88835659
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it1.3944.55122
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION

Ens-IDDom-IDAuth asym-IDNumberTypeRms dev position (Å)Weight position
11H844medium positional0.650.5
12I844medium positional0.520.5
13J844medium positional0.470.5
14K844medium positional0.550.5
21L848medium positional0.390.5
22M848medium positional0.310.5
23N848medium positional0.310.5
24O848medium positional0.340.5
31A300medium positional0.250.5
32B300medium positional0.250.5
33C300medium positional0.270.5
34D300medium positional0.280.5
11H717loose positional0.825
12I717loose positional0.725
13J717loose positional0.685
14K717loose positional0.695
21L753loose positional0.645
22M753loose positional0.65
23N753loose positional0.615
24O753loose positional0.665
31A297loose positional0.625
32B297loose positional0.755
33C297loose positional0.775
34D297loose positional0.695
11H844medium thermal0.432
12I844medium thermal0.442
13J844medium thermal0.362
14K844medium thermal0.452
21L848medium thermal0.352
22M848medium thermal0.272
23N848medium thermal0.362
24O848medium thermal0.362
31A300medium thermal0.422
32B300medium thermal0.352
33C300medium thermal0.412
34D300medium thermal0.32
11H717loose thermal0.8710
12I717loose thermal0.8210
13J717loose thermal0.5410
14K717loose thermal0.7410
21L753loose thermal0.5410
22M753loose thermal0.4310
23N753loose thermal0.5310
24O753loose thermal0.5810
31A297loose thermal0.6910
32B297loose thermal0.5110
33C297loose thermal0.7510
34D297loose thermal0.4810
LS refinement shellResolution: 2.63→2.7 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.332 297 -
Rwork0.253 5433 -
obs--98.25 %
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)
14.1069-0.3823-0.0921.57910.08261.08940.0750.10420.0354-0.1769-0.0847-0.090.0140.00980.00960.11040.00210.03020.15480.0320.1887113.2523-0.8011-29.981
23.05772.0398-0.95253.8354-0.78932.18270.06370.0863-0.3725-0.23970.0148-0.06040.4257-0.2668-0.07850.2107-0.044-0.06260.21510.07690.335122.299-30.6071-25.9188
31.3308-0.55220.74373.9703-1.31812.1327-0.0119-0.22470.05830.2999-0.111-0.0629-0.0146-0.23940.1230.095-0.09660.0190.2514-0.02080.1323105.9176-1.3621-9.1952
43.0383-0.7142-0.78412.41240.25422.06510.0952-0.1712-0.31510.0135-0.0421-0.01930.22730.0654-0.05310.1114-0.0893-0.07530.14580.14630.2353130.3353-31.4628-11.4917
53.3518-1.0525-0.0931.82880.0751.2083-0.06730.0860.1072-0.12480.03610.0172-0.02760.02780.03120.1727-0.0157-0.04710.0978-0.0090.150366.16931.9504-31.1849
61.44541.84660.74443.7832-0.28361.6006-0.0457-0.0330.0262-0.0780.08730.03690.0133-0.0126-0.04160.0620.03240.020.1025-0.0350.163558.431764.4989-30.7628
70.84290.37680.14653.57940.82711.1578-0.1682-0.17790.11930.0540.1013-0.1314-0.0332-0.03010.06690.11280.0633-0.06190.1581-0.0520.162276.290736.037-11.7471
83.4768-0.92472.11711.9692-0.76983.78680.0622-0.07040.16160.1510.04090.0016-0.0436-0.1156-0.10310.03650.01490.03540.0663-0.0240.089752.081166.5542-15.9861
92.65080.5877-0.9732.1846-0.63132.83230.0308-0.03850.0813-0.0387-0.1979-0.42020.07940.33180.16710.27870.02920.01940.38320.050.335284.786-8.1587-92.7582
104.8919-2.673-0.69785.04270.69051.5416-0.1416-0.44250.41260.32850.0873-0.3475-0.3977-0.13620.05430.51870.081-0.01740.52580.0080.446588.200820.933-102.3358
112.2851-0.97221.1163.8443-1.62812.67230.0970.0061-0.1212-0.2992-0.12750.28260.1659-0.23010.03050.27240.05120.00650.3611-0.09610.160864.4522-7.3669-101.4024
122.82590.1713-0.40693.3345-0.21142.5929-0.05850.55060.3409-0.1905-0.0136-0.1818-0.44050.0740.07210.48940.0827-0.01170.51710.06510.333182.615922.5404-118.055
132.0660.7427-0.72551.8886-0.9672.0681-0.01650.0181-0.04140.0180.0254-0.07420.05210.1046-0.00890.30650.0314-0.0290.1458-0.02490.126554.3974-41.4758-57.4069
140.7182-1.1781-0.24915.57512.07372.6568-0.02550.11460.0573-0.20010.07240.1328-0.0696-0.0539-0.04690.1675-0.02320.01930.08820.01030.10248.8883-73.3439-51.7623
151.26290.56190.75873.10670.51661.83360.04040.2118-0.0494-0.23160.0492-0.02250.2856-0.0672-0.08960.33-0.005-0.01930.1822-0.0140.101646.8362-45.4845-77.9642
161.73110.0265-0.45762.7033-0.95085.6314-0.12170.1266-0.1039-0.35250.07320.3733-0.022-0.20160.04850.1601-0.0406-0.09210.09550.01030.211333.6491-75.9459-57.2492
172.5097-0.9289-1.23583.88392.02924.2612-0.13010.4172-0.2409-0.43360.02610.10230.1728-0.19990.1040.1315-0.0231-0.05530.215-0.05630.238783.745210.3533-37.5294
182.4132-0.70080.43192.7945-0.45842.9572-0.00730.39760.2647-0.5306-0.0656-0.1563-0.1515-0.00050.07290.1532-0.02970.05690.2137-0.01830.20194.912517.9148-37.6337
194.16871.94810.24933.12420.62391.22880.0916-0.40630.04770.2772-0.0018-0.3097-0.24540.3017-0.08970.3827-0.01720.0120.3383-0.01650.13970.271-20.044-66.6011
202.05871.04190.24973.1652-0.40193.5909-0.0303-0.2253-0.17630.1997-0.0769-0.50390.16920.42760.10720.240.04160.06420.3482-0.0380.291377.89-27.5661-74.9587
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1H1 - 118
2X-RAY DIFFRACTION2H119 - 216
3X-RAY DIFFRACTION3L2 - 112
4X-RAY DIFFRACTION4L113 - 210
5X-RAY DIFFRACTION5I2 - 118
6X-RAY DIFFRACTION6I119 - 216
7X-RAY DIFFRACTION7M2 - 112
8X-RAY DIFFRACTION8M113 - 212
9X-RAY DIFFRACTION9J1 - 118
10X-RAY DIFFRACTION10J119 - 213
11X-RAY DIFFRACTION11N2 - 112
12X-RAY DIFFRACTION12N113 - 210
13X-RAY DIFFRACTION13K2 - 118
14X-RAY DIFFRACTION14K119 - 215
15X-RAY DIFFRACTION15O2 - 112
16X-RAY DIFFRACTION16O113 - 212
17X-RAY DIFFRACTION17A36 - 128
18X-RAY DIFFRACTION18B37 - 128
19X-RAY DIFFRACTION19C39 - 128
20X-RAY DIFFRACTION20D38 - 128

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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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