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- PDB-4laj: Crystal structure of HIV-1 YU2 envelope gp120 glycoprotein in com... -

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Basic information

Entry
Database: PDB / ID: 4laj
TitleCrystal structure of HIV-1 YU2 envelope gp120 glycoprotein in complex with CD4-mimetic miniprotein, M48U1, and llama single-domain, broadly neutralizing, co-receptor binding site antibody, JM4
Components
  • CD4-mimetic miniprotein M48U1
  • HIV-1 YU2 gp120 envelope glycoprotein
  • Llama single domain antibody, JM4
KeywordsVIRAL PROTEIN/INHIBITOR / CD4-induced antibody / HIV-1 neutralizing antibody / HIV-1 gp120 reactive / VIRAL PROTEIN-INHIBITOR complex
Function / homology
Function and homology information


Dectin-2 family / immunoglobulin complex / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / viral protein processing ...Dectin-2 family / immunoglobulin complex / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / structural molecule activity / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
HIV Envelope Protein Gp120; Chain G / Human immunodeficiency virus 1, Gp160, envelope glycoprotein / Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Beta Complex / Immunoglobulin V-Type ...HIV Envelope Protein Gp120; Chain G / Human immunodeficiency virus 1, Gp160, envelope glycoprotein / Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Beta Complex / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulins / Immunoglobulin-like fold / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
CD4-MIMETIC MINIPROTEIN M48U1 / 6-AMINOHEXANOIC ACID / Hi113 protein / Envelope glycoprotein gp160
Similarity search - Component
Biological speciesHuman immunodeficiency virus 1
Lama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.14 Å
AuthorsAcharya, P. / Luongo, T.S. / Kwong, P.D.
CitationJournal: J.Virol. / Year: 2013
Title: Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites.
Authors: Acharya, P. / Luongo, T.S. / Georgiev, I.S. / Matz, J. / Schmidt, S.D. / Louder, M.K. / Kessler, P. / Yang, Y. / McKee, K. / O'Dell, S. / Chen, L. / Baty, D. / Chames, P. / Martin, L. / ...Authors: Acharya, P. / Luongo, T.S. / Georgiev, I.S. / Matz, J. / Schmidt, S.D. / Louder, M.K. / Kessler, P. / Yang, Y. / McKee, K. / O'Dell, S. / Chen, L. / Baty, D. / Chames, P. / Martin, L. / Mascola, J.R. / Kwong, P.D.
History
DepositionJun 20, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 14, 2013Provider: repository / Type: Initial release
Revision 1.1Aug 21, 2013Group: Structure summary
Revision 1.2Sep 4, 2013Group: Database references
Revision 1.3Apr 9, 2014Group: Source and taxonomy
Revision 1.4Jul 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_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.pdbx_value_order / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.5Sep 20, 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 / struct_ncs_dom_lim
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id
Revision 2.0Nov 15, 2023Group: Atomic model / Data collection / Category: atom_site / chem_comp_atom / chem_comp_bond
Item: _atom_site.auth_atom_id / _atom_site.label_atom_id ..._atom_site.auth_atom_id / _atom_site.label_atom_id / _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_1 / _chem_comp_bond.atom_id_2

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
J: HIV-1 YU2 gp120 envelope glycoprotein
F: HIV-1 YU2 gp120 envelope glycoprotein
A: HIV-1 YU2 gp120 envelope glycoprotein
B: HIV-1 YU2 gp120 envelope glycoprotein
K: CD4-mimetic miniprotein M48U1
D: CD4-mimetic miniprotein M48U1
G: CD4-mimetic miniprotein M48U1
C: CD4-mimetic miniprotein M48U1
H: Llama single domain antibody, JM4
M: Llama single domain antibody, JM4
L: Llama single domain antibody, JM4
I: Llama single domain antibody, JM4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)243,35955
Polymers235,05112
Non-polymers8,30843
Water10,269570
1
J: HIV-1 YU2 gp120 envelope glycoprotein
K: CD4-mimetic miniprotein M48U1
H: Llama single domain antibody, JM4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,81613
Polymers58,7633
Non-polymers2,05310
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3440 Å2
ΔGint-9 kcal/mol
Surface area21350 Å2
MethodPISA
2
F: HIV-1 YU2 gp120 envelope glycoprotein
G: CD4-mimetic miniprotein M48U1
M: Llama single domain antibody, JM4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,75412
Polymers58,7633
Non-polymers1,9919
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3410 Å2
ΔGint-12 kcal/mol
Surface area21360 Å2
MethodPISA
3
A: HIV-1 YU2 gp120 envelope glycoprotein
D: CD4-mimetic miniprotein M48U1
L: Llama single domain antibody, JM4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,94015
Polymers58,7633
Non-polymers2,17712
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3550 Å2
ΔGint-10 kcal/mol
Surface area21690 Å2
MethodPISA
4
B: HIV-1 YU2 gp120 envelope glycoprotein
C: CD4-mimetic miniprotein M48U1
I: Llama single domain antibody, JM4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,85015
Polymers58,7633
Non-polymers2,08712
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3520 Å2
ΔGint-12 kcal/mol
Surface area21490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)96.772, 86.221, 144.848
Angle α, β, γ (deg.)90.00, 102.88, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11chain J
12chain K
13chain M

NCS domain segments:

Dom-ID: 1 / Component-ID: 1 / End auth comp-ID: HOH / End label comp-ID: HOH

Ens-IDBeg auth comp-IDBeg label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
1VALVALchain 'J'JA - DB44 - 66625
2MPTMPTchain 'K'KE - HB1 - 1031
3GLUGLUchain 'M'MJ - MB1 - 2091

NCS ensembles :
ID
1
2
3

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Components

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Protein / Protein/peptide / Antibody / Sugars , 4 types, 47 molecules JFABKDGCHMLI

#1: Protein
HIV-1 YU2 gp120 envelope glycoprotein


Mass: 41695.406 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: YU2 / Gene: Env / Cell line (production host): HEK-293F / Production host: Homo Sapiens (human) / References: UniProt: P35961*PLUS
#2: Protein/peptide
CD4-mimetic miniprotein M48U1


Type: Peptide-like / Class: Inhibitor / Mass: 3056.804 Da / Num. of mol.: 4 / Source method: obtained synthetically / Details: CD4-mimetic miniprotein / References: CD4-MIMETIC MINIPROTEIN M48U1
#3: Antibody
Llama single domain antibody, JM4


Mass: 14010.511 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Cell line (production host): HEK-293F / Production host: Homo Sapiens (human) / References: UniProt: A2KD57*PLUS
#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 / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 35
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

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Non-polymers , 3 types, 578 molecules

#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-ACA / 6-AMINOHEXANOIC ACID / AMINOCAPROIC ACID / Aminocaproic acid


Type: peptide linking / Mass: 131.173 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H13NO2 / Comment: inhibitor*YM
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 570 / Source method: isolated from a natural source / Formula: H2O

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Details

Compound detailsTHE CD4-MIMETIC MINIPROTEINS INHIBIT HIV-1 ENTRY AND ARE DERIVED FROM SCYLLATOXIN (A SCORPION TOXIN) ...THE CD4-MIMETIC MINIPROTEINS INHIBIT HIV-1 ENTRY AND ARE DERIVED FROM SCYLLATOXIN (A SCORPION TOXIN) BY TRANSPLANTING THE GP120-INTERACTIVE REGION OF CD4 ONTO THE SCYLLATOXIN SCAFFOLD, FOLLOWED BY MANY ROUNDS OF ITERATIVE OPTIMIZATION

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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: 50.92 %
Crystal growTemperature: 298 K / pH: 8
Details: PEG 3000 28% w/v, 0.2 M lithium sulfate monohydrate, 0.1M imidazole, pH 8.0, 30% w/v 6-aminohexanoic acid , VAPOR DIFFUSION, HANGING DROP, temperature 298K

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Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Details: SI (111)
RadiationMonochromator: SI 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.14→50 Å / Num. obs: 99049 / % possible obs: 78 % / Observed criterion σ(I): 2 / Redundancy: 4.5 % / Rsym value: 0.106 / Net I/σ(I): 11.4
Reflection shellResolution: 2.14→2.17 Å / Redundancy: 2.3 % / Mean I/σ(I) obs: 1.2 / Rsym value: 0.46 / % possible all: 45.1

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Processing

Software
NameVersionClassification
HKL-2000data collection
PHASERphasing
PHENIX(phenix.refine: 1.8.2_1309)refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3ROM and 4JZZ
Resolution: 2.14→38.8 Å / SU ML: 0.26 / Isotropic thermal model: Isotropic / σ(F): 1.34 / Phase error: 27.88 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.227 4969 5.03 %
Rwork0.185 --
obs0.188 98838 76.7 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.14→38.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15223 0 527 570 16320
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00516225
X-RAY DIFFRACTIONf_angle_d1.00321922
X-RAY DIFFRACTIONf_dihedral_angle_d12.9195955
X-RAY DIFFRACTIONf_chiral_restr0.1812498
X-RAY DIFFRACTIONf_plane_restr0.0042772
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDTypeRms dev position (Å)
11J6459X-RAY DIFFRACTIONPOSITIONAL7.758
21K381X-RAY DIFFRACTIONPOSITIONAL7.758
31M1692X-RAY DIFFRACTIONPOSITIONAL7.758
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.14-2.16070.3248700.2261329X-RAY DIFFRACTION32
2.1607-2.18620.2719910.22971839X-RAY DIFFRACTION45
2.1862-2.21280.29381030.22281912X-RAY DIFFRACTION48
2.2128-2.24080.2787860.23682063X-RAY DIFFRACTION50
2.2408-2.27030.29281180.2232009X-RAY DIFFRACTION50
2.2703-2.30140.25781070.21622168X-RAY DIFFRACTION53
2.3014-2.33430.26821280.19992133X-RAY DIFFRACTION53
2.3343-2.36910.3551030.21542280X-RAY DIFFRACTION56
2.3691-2.40610.26891370.22832335X-RAY DIFFRACTION58
2.4061-2.44560.26091160.22632442X-RAY DIFFRACTION60
2.4456-2.48770.26941270.22212561X-RAY DIFFRACTION63
2.4877-2.5330.29351480.21752739X-RAY DIFFRACTION67
2.533-2.58170.28811600.2172873X-RAY DIFFRACTION71
2.5817-2.63440.29851500.22713036X-RAY DIFFRACTION74
2.6344-2.69160.26971870.22953181X-RAY DIFFRACTION78
2.6916-2.75420.24491640.22323376X-RAY DIFFRACTION83
2.7542-2.82310.26652270.22733449X-RAY DIFFRACTION86
2.8231-2.89940.2831930.21753621X-RAY DIFFRACTION89
2.8994-2.98470.27781710.22053771X-RAY DIFFRACTION92
2.9847-3.0810.2962130.22313949X-RAY DIFFRACTION96
3.081-3.1910.2552330.21263907X-RAY DIFFRACTION97
3.191-3.31870.24232170.19484063X-RAY DIFFRACTION99
3.3187-3.46970.22722080.18774086X-RAY DIFFRACTION100
3.4697-3.65250.23881990.1784042X-RAY DIFFRACTION100
3.6525-3.88110.19292270.16924111X-RAY DIFFRACTION100
3.8811-4.18050.18332240.15084047X-RAY DIFFRACTION100
4.1805-4.60060.182130.13524103X-RAY DIFFRACTION99
4.6006-5.26490.16842340.13624068X-RAY DIFFRACTION100
5.2649-6.62780.2072040.17734153X-RAY DIFFRACTION100
6.6278-38.80960.19922110.18714223X-RAY DIFFRACTION100
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)
11.22630.3516-0.15941.6922-0.03391.1021-0.10940.1443-0.1711-0.28430.01780.12450.0965-0.13640.08530.3219-0.00310.10020.254-0.02810.5286-11.31390.1873-69.4121
22.94290.43542.13264.84540.76324.43070.034-0.0302-0.0863-0.0405-0.02070.22050.4035-0.0270.01940.3688-0.01320.1450.2703-0.00330.375-32.103532.9711-25.9635
31.24090.0294-0.06361.7053-0.00781.84560.10490.18560.1525-0.29270.0166-0.0946-0.17770.0288-0.11920.38920.02490.16250.3026-0.0060.4514-32.7723-7.9658-22.778
42.21180.42711.11573.7997-1.15545.612-0.07660.37250.3678-0.3130.05780.0437-0.08110.09250.01810.2406-0.01240.07530.29970.08810.4184-13.39744.2456-81.6369
51.0136-0.10190.38911.52540.40692.27110.0043-0.1103-0.10550.48450.0809-0.22480.00050.2672-0.08250.496-0.00290.04830.3231-0.02080.4538-20.399445.8724.3249
63.3295-0.70041.84794.2788-0.37335.3387-0.043-0.3446-0.33120.3580.0504-0.43910.23150.167900.31960.06440.05620.32940.11090.58455.7406-6.7224-40.5729
71.1266-0.1280.00421.2062-0.01491.108-0.0281-0.12790.11440.18030.0319-0.0806-0.07170.03080.01020.2844-0.00780.09550.2093-0.00630.4205-1.944336.7832-50.0493
82.34240.84961.12515.3931.35986.52390.082-0.86420.66951.1619-0.016-0.6236-0.42160.375-0.07410.7048-0.0504-0.06990.6417-0.24920.7243-20.79233.69687.7747
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain A or chain D
2X-RAY DIFFRACTION2chain H
3X-RAY DIFFRACTION3chain F or chain G
4X-RAY DIFFRACTION4chain I
5X-RAY DIFFRACTION5chain J or chain K
6X-RAY DIFFRACTION6chain L
7X-RAY DIFFRACTION7chain B or chain C
8X-RAY DIFFRACTION8chain M

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