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- PDB-3qb7: Interleukin-4 mutant RGA bound to cytokine receptor common gamma -

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Basic information

Entry
Database: PDB / ID: 3qb7
TitleInterleukin-4 mutant RGA bound to cytokine receptor common gamma
Components
  • Cytokine receptor common subunit gamma
  • Interleukin 4
KeywordsCYTOKINE/CYTOKINE RECEPTOR / cytokine signaling / IL-4Ralpha / CYTOKINE-CYTOKINE RECEPTOR complex
Function / homology
Function and homology information


interleukin-7-mediated signaling pathway / mature B cell differentiation / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / interleukin-4 receptor binding / positive regulation of isotype switching to IgE isotypes / positive regulation of eosinophil chemotaxis / B cell costimulation / negative regulation of complement-dependent cytotoxicity ...interleukin-7-mediated signaling pathway / mature B cell differentiation / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / interleukin-4 receptor binding / positive regulation of isotype switching to IgE isotypes / positive regulation of eosinophil chemotaxis / B cell costimulation / negative regulation of complement-dependent cytotoxicity / negative regulation of macrophage activation / negative regulation of chronic inflammatory response / Interleukin-18 signaling / regulation of isotype switching / negative regulation of neuroinflammatory response / positive regulation of T cell differentiation in thymus / positive regulation of cellular respiration / negative regulation of epithelial cell migration / negative regulation of T-helper 17 cell differentiation / dendritic cell differentiation / positive regulation of T-helper 2 cell cytokine production / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / positive regulation of isotype switching to IgG isotypes / positive regulation of amyloid-beta clearance / neuroinflammatory response / interleukin-4-mediated signaling pathway / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-2-mediated signaling pathway / macrophage activation / myeloid dendritic cell differentiation / positive regulation of mast cell degranulation / positive regulation of mononuclear cell migration / regulation of phosphorylation / type 2 immune response / STAT3 nuclear events downstream of ALK signaling / activation of Janus kinase activity / interleukin-15-mediated signaling pathway / positive regulation of MHC class II biosynthetic process / T-helper 2 cell differentiation / Interleukin-15 signaling / cytokine receptor activity / Interleukin-2 signaling / negative regulation of cellular response to transforming growth factor beta stimulus / positive regulation of T cell differentiation / positive regulation of B cell differentiation / positive regulation of interleukin-13 production / B cell activation / positive regulation of myoblast fusion / cytokine binding / positive regulation of ATP biosynthetic process / negative regulation of osteoclast differentiation / positive regulation of macroautophagy / positive regulation of interleukin-10 production / negative regulation of acute inflammatory response / negative regulation of tumor necrosis factor production / regulation of immune response / Interleukin receptor SHC signaling / coreceptor activity / positive regulation of phagocytosis / negative regulation of endothelial cell apoptotic process / positive regulation of B cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of defense response to virus by host / extrinsic apoptotic signaling pathway in absence of ligand / cholesterol metabolic process / positive regulation of T cell proliferation / Interleukin-7 signaling / T cell activation / B cell differentiation / innate immune response in mucosa / cytokine activity / negative regulation of extrinsic apoptotic signaling pathway / microglial cell activation / growth factor activity / negative regulation of inflammatory response / positive regulation of receptor-mediated endocytosis / cytokine-mediated signaling pathway / gene expression / T cell differentiation in thymus / positive regulation of cold-induced thermogenesis / RAF/MAP kinase cascade / Interleukin-4 and Interleukin-13 signaling / receptor complex / endosome / positive regulation of cell migration / immune response / external side of plasma membrane / negative regulation of DNA-templated transcription / positive regulation of cell population proliferation / positive regulation of gene expression / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / cell surface / endoplasmic reticulum / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space
Similarity search - Function
: / : / Cytokine receptor-like factor 2-like, D1 domain / Cytokine receptor-like factor 2-like, D2 domain / Interleukin-4 / Interleukin 4 / Interleukin-4/interleukin-13 / Interleukin-4/interleukin-13, conserved site / Interleukins -4 and -13 signature. / Interleukins 4 and 13 ...: / : / Cytokine receptor-like factor 2-like, D1 domain / Cytokine receptor-like factor 2-like, D2 domain / Interleukin-4 / Interleukin 4 / Interleukin-4/interleukin-13 / Interleukin-4/interleukin-13, conserved site / Interleukins -4 and -13 signature. / Interleukins 4 and 13 / Short hematopoietin receptor family 1 signature. / Interleukin-6 receptor alpha chain, binding / Short hematopoietin receptor, family 1, conserved site / Growth Hormone; Chain: A; - #10 / Four-helical cytokine-like, core / Growth Hormone; Chain: A; / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulins / Immunoglobulin-like fold / Up-down Bundle / Immunoglobulin-like / Sandwich / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Interleukin-4 / Interleukin-4 / Cytokine receptor common subunit gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.245 Å
AuthorsBates, D.L. / Junttila, I.S. / Creusot, R.J. / Moraga, I. / Lupardus, P. / Fathman, C.G. / Paul, W.E. / Garcia, K.C.
CitationJournal: Nat.Chem.Biol. / Year: 2012
Title: Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines.
Authors: Junttila, I.S. / Creusot, R.J. / Moraga, I. / Bates, D.L. / Wong, M.T. / Alonso, M.N. / Suhoski, M.M. / Lupardus, P. / Meier-Schellersheim, M. / Engleman, E.G. / Utz, P.J. / Fathman, C.G. / ...Authors: Junttila, I.S. / Creusot, R.J. / Moraga, I. / Bates, D.L. / Wong, M.T. / Alonso, M.N. / Suhoski, M.M. / Lupardus, P. / Meier-Schellersheim, M. / Engleman, E.G. / Utz, P.J. / Fathman, C.G. / Paul, W.E. / Garcia, K.C.
History
DepositionJan 12, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 25, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 14, 2012Group: Database references
Revision 1.2Dec 12, 2012Group: Database references
Revision 1.3Nov 8, 2017Group: Advisory / Refinement description / Category: pdbx_unobs_or_zero_occ_atoms / software / Item: _software.name
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_validate_close_contact / struct_asym / struct_conn / struct_ref_seq_dif / struct_site / struct_site_gen
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 / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _chem_comp.type / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_asym_id_2 / _pdbx_validate_close_contact.auth_seq_id_1 / _pdbx_validate_close_contact.auth_seq_id_2 / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _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 / _struct_ref_seq_dif.details
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Dec 27, 2023Group: Advisory / Data collection ...Advisory / Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms / struct_conn
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: Interleukin 4
B: Interleukin 4
C: Cytokine receptor common subunit gamma
D: Cytokine receptor common subunit gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)80,63110
Polymers79,1474
Non-polymers1,4836
Water0
1
A: Interleukin 4
D: Cytokine receptor common subunit gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,3155
Polymers39,5742
Non-polymers7423
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Interleukin 4
C: Cytokine receptor common subunit gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,3155
Polymers39,5742
Non-polymers7423
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)75.969, 105.879, 121.093
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Interleukin 4 /


Mass: 15264.575 Da / Num. of mol.: 2 / Fragment: UNP residues 25-153
Mutation: K117R, T118V, R121Q, E122S, Y124W, S125F, S128G, S129A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: D4HNR6, UniProt: P05112*PLUS
#2: Protein Cytokine receptor common subunit gamma / Interleukin-2 receptor subunit gamma / IL-2 receptor subunit gamma / IL-2R subunit gamma / IL-2RG / p64


Mass: 24309.121 Da / Num. of mol.: 2 / Fragment: UNP residues 55-254 / Mutation: N53Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2RG / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P31785
#3: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#4: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#5: 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.: 2
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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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.94 Å3/Da / Density % sol: 58.17 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.3
Details: 100 mM (NH4)2SO4, 100 mM Cacodylate, 20% PEG-3350, pH 6.3, VAPOR DIFFUSION, SITTING DROP, temperature 298K

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Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.2 / Wavelength: 0.97 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 20, 2010
RadiationMonochromator: U50 Undulator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 3.25→100 Å / Num. all: 16040 / Num. obs: 16040 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1.8 / Redundancy: 7.9 % / Rmerge(I) obs: 0.153 / Net I/σ(I): 5
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
3.25-3.377.91199.9
3.37-3.58.10.8191100
3.5-3.668.10.5311100
3.66-3.858.10.3931100
3.85-4.098.10.2831100
4.09-4.4180.1981100
4.41-4.8580.131100
4.85-5.567.90.1121100
5.56-77.70.1071100
7-1007.30.046199.5

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Phasing

PhasingMethod: molecular replacement

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Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
PHASERphasing
PHENIXdev_613refinement
PDB_EXTRACT3.1data extraction
ADSCQuantumdata collection
DENZOdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.245→48.507 Å / Occupancy max: 1 / Occupancy min: 0 / SU ML: 0.39 / σ(F): 0 / Phase error: 28.98 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2922 799 5 %
Rwork0.2309 --
obs0.2339 15980 99.78 %
all-15980 -
Solvent computationShrinkage radii: 0.83 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 55.318 Å2 / ksol: 0.303 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--6.387 Å2-0 Å20 Å2
2---9.9821 Å2-0 Å2
3---16.3691 Å2
Refinement stepCycle: LAST / Resolution: 3.245→48.507 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5222 0 94 0 5316
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0035488
X-RAY DIFFRACTIONf_angle_d1.3247424
X-RAY DIFFRACTIONf_dihedral_angle_d14.7882041
X-RAY DIFFRACTIONf_chiral_restr0.06807
X-RAY DIFFRACTIONf_plane_restr0.003930
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.2454-3.44870.34781320.30372461X-RAY DIFFRACTION99
3.4487-3.71480.31961370.25592489X-RAY DIFFRACTION100
3.7148-4.08850.34611340.22232488X-RAY DIFFRACTION100
4.0885-4.67970.26211480.19312500X-RAY DIFFRACTION100
4.6797-5.89430.24741280.20082568X-RAY DIFFRACTION100
5.8943-48.5120.29511200.24772675X-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)
11.58990.27770.43560.65021.04531.88480.49390.4132-0.1645-0.1546-0.0255-0.0274-0.1916-0.0964-0.37240.47370.1353-0.08590.71430.15860.5717-58.56898.795816.1203
21.29670.1006-0.77930.8190.0050.49640.0858-0.64380.07060.08150.19120.27860.00470.11840.11140.3684-0.02540.02240.54150.36070.4238-64.92062.751224.8548
31.2512-1.632-0.79892.28191.77675.6729-0.3295-0.087-0.56580.2133-0.44320.42720.0920.11590.67170.7802-0.09350.04470.63880.13190.9907-60.072.38445.5927
40.40690.0787-0.01110.42050.30070.32080.26350.07890.10020.21850.03260.1368-0.74320.0492-0.14070.53060.01140.09070.76590.25760.3705-26.516523.436314.0862
53.0803-0.9461-0.08841.84350.81051.08660.22740.0586-0.62990.0799-0.59220.1478-0.0126-0.33120.32720.5279-0.0421-0.04180.96450.10120.6814-29.60928.166112.765
63.9507-1.7447-1.22522.9469-1.47663.49740.1039-0.0036-0.58320.0916-0.10090.82780.0929-0.2019-0.00790.3116-0.02620.02640.41840.0870.6474-19.1860.540415.7296
70.3203-0.22440.07750.66240.38160.3653-0.0383-0.0311-0.317-0.2662-0.20440.15820.0699-0.0914-0.06880.4824-0.020.11530.53670.22960.4902-18.44589.958314.0651
80.29940.10350.00060.38030.01510.15930.2182-0.0592-0.2345-0.36770.1348-0.44210.08750.08690.55430.275-0.15240.1857-0.15570.39480.7665-41.069-13.49875.6383
90.8736-0.1008-0.00920.838-0.69730.6093-0.0633-0.18730.3309-0.1998-0.1906-0.25280.17330.28-0.0010.34520.0338-0.01280.36830.23290.4401-42.398219.3192-1.5252
100.9443-0.4052-0.13150.65250.60860.75960.0368-0.09650.34280.0605-0.214-0.07320.15520.13640.10850.468-0.0179-0.04210.7620.10980.4493-38.70689.520140.6112
110.37290.3996-0.33720.7772-0.27791.1763-0.1747-0.07950.46470.1990.07630.3479-0.12290.41450.09880.48790.0024-0.13930.59280.18560.7086-49.909928.433417.3332
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resseq 3:22)
2X-RAY DIFFRACTION2chain 'A' and (resseq 23:119)
3X-RAY DIFFRACTION3chain 'A' and (resseq 120:127)
4X-RAY DIFFRACTION4chain 'B' and (resseq 3:12)
5X-RAY DIFFRACTION5chain 'B' and (resseq 13:22)
6X-RAY DIFFRACTION6chain 'B' and (resseq 23:32)
7X-RAY DIFFRACTION7chain 'B' and (resseq 33:127)
8X-RAY DIFFRACTION8chain 'C' and (resseq 33:135)
9X-RAY DIFFRACTION9chain 'C' and (resseq 136:226)
10X-RAY DIFFRACTION10chain 'D' and (resseq 33:137)
11X-RAY DIFFRACTION11chain 'D' and (resseq 138:226)

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