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- PDB-5m8t: Crystal structure of human tyrosinase related protein 1 (T391V-R3... -

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Basic information

Entry
Database: PDB / ID: 5m8t
TitleCrystal structure of human tyrosinase related protein 1 (T391V-R374S-Y362F) in complex with tropolone
Components5,6-dihydroxyindole-2-carboxylic acid oxidase
KeywordsUNKNOWN FUNCTION / human tyrosinase related protein 1 / melanin biosynthesis / tyrosinase / oxidoreductase
Function / homology
Function and homology information


Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With another compound as one donor, and incorporation of one atom of oxygen into the other donor / acetoacetic acid metabolic process / Melanin biosynthesis / positive regulation of melanin biosynthetic process / tyrosinase activity / melanocyte differentiation / melanin biosynthetic process / melanosome membrane / melanosome organization / intracellular vesicle ...Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With another compound as one donor, and incorporation of one atom of oxygen into the other donor / acetoacetic acid metabolic process / Melanin biosynthesis / positive regulation of melanin biosynthetic process / tyrosinase activity / melanocyte differentiation / melanin biosynthetic process / melanosome membrane / melanosome organization / intracellular vesicle / clathrin-coated endocytic vesicle membrane / melanosome / oxidoreductase activity / endosome membrane / protein homodimerization activity / metal ion binding / cytoplasm
Similarity search - Function
Tyrosinase CuA-binding region signature. / Common central domain of tyrosinase / Tyrosinase and hemocyanins CuB-binding region signature. / Tyrosinase copper-binding domain / Di-copper centre-containing domain superfamily
Similarity search - Domain/homology
2-HYDROXYCYCLOHEPTA-2,4,6-TRIEN-1-ONE / 5,6-dihydroxyindole-2-carboxylic acid oxidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.35 Å
AuthorsLai, X. / Soler-Lopez, M. / Wichers, H.J. / Dijkstra, B.W.
CitationJournal: Angew. Chem. Int. Ed. Engl. / Year: 2017
Title: Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis.
Authors: Lai, X. / Wichers, H.J. / Soler-Lopez, M. / Dijkstra, B.W.
History
DepositionOct 29, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 12, 2017Provider: repository / Type: Initial release
Revision 1.1Aug 9, 2017Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Oct 16, 2019Group: Data collection / Category: chem_comp / reflns_shell / Item: _chem_comp.type
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / 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_struct_conn_angle / pdbx_validate_close_contact / struct_asym / struct_conn / 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_struct_assembly_gen.asym_id_list / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _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.conn_type_id / _struct_conn.id / _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
Description: Carbohydrate remediation / Provider: repository / Type: Remediation

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: 5,6-dihydroxyindole-2-carboxylic acid oxidase
B: 5,6-dihydroxyindole-2-carboxylic acid oxidase
C: 5,6-dihydroxyindole-2-carboxylic acid oxidase
D: 5,6-dihydroxyindole-2-carboxylic acid oxidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)213,37837
Polymers202,1254
Non-polymers11,25333
Water10,395577
1
A: 5,6-dihydroxyindole-2-carboxylic acid oxidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,7929
Polymers50,5311
Non-polymers2,2618
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: 5,6-dihydroxyindole-2-carboxylic acid oxidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,4829
Polymers50,5311
Non-polymers2,9508
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: 5,6-dihydroxyindole-2-carboxylic acid oxidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,43610
Polymers50,5311
Non-polymers2,9049
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: 5,6-dihydroxyindole-2-carboxylic acid oxidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,6699
Polymers50,5311
Non-polymers3,1388
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)89.732, 140.605, 191.253
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resseq 25:33 or resseq 35:36 or resseq...
21(chain B and (resseq 25:33 or resseq 35:36 or resseq...
31(chain D and (resseq 25:33 or resseq 35:36 or resseq...

NCS domain segments:
Dom-IDComponent-IDEns-IDSelection detailsAuth asym-IDAuth seq-ID
111(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 33
121(chain A and (resseq 25:33 or resseq 35:36 or resseq...A35 - 36
131(chain A and (resseq 25:33 or resseq 35:36 or resseq...A38 - 47
141(chain A and (resseq 25:33 or resseq 35:36 or resseq...A49 - 63
151(chain A and (resseq 25:33 or resseq 35:36 or resseq...A65 - 113
161(chain A and (resseq 25:33 or resseq 35:36 or resseq...A115 - 117
171(chain A and (resseq 25:33 or resseq 35:36 or resseq...A119 - 134
181(chain A and (resseq 25:33 or resseq 35:36 or resseq...A135
191(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
1101(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
1111(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
1121(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
1131(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
1141(chain A and (resseq 25:33 or resseq 35:36 or resseq...A25 - 3852
211(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 33
221(chain B and (resseq 25:33 or resseq 35:36 or resseq...B35 - 36
231(chain B and (resseq 25:33 or resseq 35:36 or resseq...B38 - 47
241(chain B and (resseq 25:33 or resseq 35:36 or resseq...B49 - 63
251(chain B and (resseq 25:33 or resseq 35:36 or resseq...B65 - 113
261(chain B and (resseq 25:33 or resseq 35:36 or resseq...B115 - 117
271(chain B and (resseq 25:33 or resseq 35:36 or resseq...B119 - 134
281(chain B and (resseq 25:33 or resseq 35:36 or resseq...B135
291(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
2101(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
2111(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
2121(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
2131(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
2141(chain B and (resseq 25:33 or resseq 35:36 or resseq...B25 - 3852
311(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 33
321(chain D and (resseq 25:33 or resseq 35:36 or resseq...D35 - 36
331(chain D and (resseq 25:33 or resseq 35:36 or resseq...D38 - 47
341(chain D and (resseq 25:33 or resseq 35:36 or resseq...D49 - 63
351(chain D and (resseq 25:33 or resseq 35:36 or resseq...D65 - 113
361(chain D and (resseq 25:33 or resseq 35:36 or resseq...D115 - 117
371(chain D and (resseq 25:33 or resseq 35:36 or resseq...D119 - 134
381(chain D and (resseq 25:33 or resseq 35:36 or resseq...D135
391(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852
3101(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852
3111(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852
3121(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852
3131(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852
3141(chain D and (resseq 25:33 or resseq 35:36 or resseq...D25 - 3852

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Components

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Protein , 1 types, 4 molecules ABCD

#1: Protein
5,6-dihydroxyindole-2-carboxylic acid oxidase / DHICA oxidase / Catalase B / Glycoprotein 75 / Melanoma antigen gp75 / Tyrosinase-related protein 1 / TRP1


Mass: 50531.160 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TYRP1, CAS2, TYRP, TYRRP / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P17643, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With another compound as one donor, and incorporation of one atom of oxygen into the other donor

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Sugars , 7 types, 21 molecules

#2: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 570.542 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-1-2/a4-b1_a6-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#3: Polysaccharide alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
LFucpa1-6DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-2/a6-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#4: 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.: 9
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
#5: Polysaccharide alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 894.823 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-6DManpa1-4DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/3,5,4/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1a_1-5][a1221m-1a_1-5]/1-1-2-2-3/a4-b1_a6-e1_b4-c1_c6-d1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][a-D-Manp]{[(6+1)][a-D-Manp]{}}}[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#6: Polysaccharide alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1a_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#7: Polysaccharide alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 732.682 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-4DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/3,4,3/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1a_1-5][a1221m-1a_1-5]/1-1-2-3/a4-b1_a6-d1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][a-D-Manp]{}}[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#8: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose


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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Non-polymers , 3 types, 589 molecules

#9: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#10: Chemical
ChemComp-0TR / 2-HYDROXYCYCLOHEPTA-2,4,6-TRIEN-1-ONE / TROPOLONE


Mass: 122.121 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C7H6O2
#11: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 577 / 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: 2.98 Å3/Da / Density % sol: 58.79 %
Crystal growTemperature: 290 K / Method: vapor diffusion, sitting drop
Details: 0.1 M Tris (pH 7.0), 0.2 M NaCl and 30% (w/v) PEG 3000

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 1, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 2.35→48.75 Å / Num. obs: 100975 / % possible obs: 99.7 % / Redundancy: 4.3 % / Net I/σ(I): 11.9

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Processing

Software
NameVersionClassification
PDB_EXTRACT3.2data extraction
PHENIXrefinement
SCALAdata scaling
PHENIXphasing
RefinementResolution: 2.35→48.747 Å / SU ML: 0.3 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 23.82
RfactorNum. reflection% reflection
Rfree0.2254 4972 4.93 %
Rwork0.1828 --
obs0.185 100890 99.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 99.23 Å2 / Biso mean: 43.5907 Å2 / Biso min: 21.86 Å2
Refinement stepCycle: final / Resolution: 2.35→48.747 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14216 0 722 577 15515
Biso mean--60.22 44.08 -
Num. residues----1784
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A6303X-RAY DIFFRACTION7.209TORSIONAL
12B6303X-RAY DIFFRACTION7.209TORSIONAL
13D6303X-RAY DIFFRACTION7.209TORSIONAL

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