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- PDB-4ma8: Crystal structure of mouse prion protein complexed with Chlorpromazine -

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Basic information

Entry
Database: PDB / ID: 4ma8
TitleCrystal structure of mouse prion protein complexed with Chlorpromazine
Components
  • Major prion protein
  • POM1 heavy chain
  • POM1 light chain
KeywordsIMMUNE SYSTEM / Immunoglobulin fold / Fab / Antibody / Mouse prion protein
Function / homology
Function and homology information


Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / negative regulation of amyloid precursor protein catabolic process / lamin binding / regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan binding / negative regulation of interleukin-17 production / ATP-dependent protein binding / regulation of potassium ion transmembrane transport ...Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / negative regulation of amyloid precursor protein catabolic process / lamin binding / regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan binding / negative regulation of interleukin-17 production / ATP-dependent protein binding / regulation of potassium ion transmembrane transport / negative regulation of dendritic spine maintenance / type 5 metabotropic glutamate receptor binding / cupric ion binding / nucleobase-containing compound metabolic process / response to copper ion / negative regulation of interleukin-2 production / negative regulation of calcineurin-NFAT signaling cascade / negative regulation of T cell receptor signaling pathway / negative regulation of amyloid-beta formation / cuprous ion binding / activation of protein kinase activity / negative regulation of activated T cell proliferation / negative regulation of long-term synaptic potentiation / response to amyloid-beta / negative regulation of type II interferon production / : / intracellular copper ion homeostasis / positive regulation of protein targeting to membrane / response to cadmium ion / side of membrane / inclusion body / regulation of peptidyl-tyrosine phosphorylation / cellular response to copper ion / molecular condensate scaffold activity / neuron projection maintenance / tubulin binding / protein sequestering activity / negative regulation of protein phosphorylation / molecular function activator activity / positive regulation of protein localization to plasma membrane / protein destabilization / protein homooligomerization / negative regulation of DNA-binding transcription factor activity / terminal bouton / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / regulation of protein localization / positive regulation of peptidyl-tyrosine phosphorylation / cellular response to xenobiotic stimulus / signaling receptor activity / amyloid-beta binding / protein-folding chaperone binding / microtubule binding / nuclear membrane / response to oxidative stress / protease binding / mitochondrial outer membrane / transmembrane transporter binding / postsynaptic density / learning or memory / molecular adaptor activity / copper ion binding / membrane raft / intracellular membrane-bounded organelle / dendrite / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / membrane / identical protein binding / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Prion protein signature 1. / Prion protein signature 2. / Major prion protein N-terminal domain / Major prion protein bPrPp - N terminal / Prion protein / Major prion protein / Prion/Doppel protein, beta-ribbon domain / Prion/Doppel beta-ribbon domain superfamily / Prion/Doppel alpha-helical domain / Immunoglobulins ...Prion protein signature 1. / Prion protein signature 2. / Major prion protein N-terminal domain / Major prion protein bPrPp - N terminal / Prion protein / Major prion protein / Prion/Doppel protein, beta-ribbon domain / Prion/Doppel beta-ribbon domain superfamily / Prion/Doppel alpha-helical domain / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Chem-Z80 / Major prion protein
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsBaral, P.K. / Swayampakula, M. / James, M.N.G.
CitationJournal: Structure / Year: 2014
Title: Structural basis of prion inhibition by phenothiazine compounds.
Authors: Baral, P.K. / Swayampakula, M. / Rout, M.K. / Kav, N.N. / Spyracopoulos, L. / Aguzzi, A. / James, M.N.
History
DepositionAug 15, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 22, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 26, 2014Group: Database references
Revision 1.2Oct 12, 2022Group: Database references / Derived calculations / Structure summary
Category: chem_comp / database_2 / struct_site
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Sep 20, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
C: Major prion protein
H: POM1 heavy chain
L: POM1 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,5874
Polymers60,2683
Non-polymers3191
Water7,999444
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)83.262, 106.883, 75.594
Angle α, β, γ (deg.)90.00, 95.32, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11C-454-

HOH

21C-488-

HOH

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Components

#1: Protein Major prion protein / PrP / PrP27-30 / PrP33-35C


Mass: 13360.877 Da / Num. of mol.: 1 / Fragment: UNP residues 116-229
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Prnp, Prn-p, Prp / Production host: Escherichia coli (E. coli) / References: UniProt: P04925
#2: Antibody POM1 heavy chain


Mass: 23397.078 Da / Num. of mol.: 1 / Fragment: Fab
Source method: isolated from a genetically manipulated source
Details: hybridoma / Source: (gene. exp.) Mus musculus (house mouse) / Cell: hybridoma
#3: Antibody POM1 light chain


Mass: 23509.701 Da / Num. of mol.: 1 / Fragment: Fab
Source method: isolated from a genetically manipulated source
Details: hybridoma / Source: (gene. exp.) Mus musculus (house mouse) / Cell: hybridoma
#4: Chemical ChemComp-Z80 / 3-(2-chloro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-amine / Chlorpromazine / Chlorpromazine


Mass: 318.864 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H19ClN2S / Comment: medication, antipsychotic*YM
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 444 / 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: 2.78 Å3/Da / Density % sol: 55.73 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 25% PEG3350, 0.1 M Bis-Tris, pH 6.5, 0.2 M lithium sulfate, VAPOR DIFFUSION, SITTING DROP, temperature 298K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 1.007 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 6, 2012
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.007 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. obs: 32491 / % possible obs: 97.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.5 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 14
Reflection shellResolution: 2.2→2.28 Å / Redundancy: 2.2 % / Rmerge(I) obs: 0.57 / Mean I/σ(I) obs: 1.5 / % possible all: 86.4

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Processing

Software
NameVersionClassification
MOLREPphasing
REFMAC5.7.0032refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4H88
Resolution: 2.2→34.99 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.93 / SU B: 12.02 / SU ML: 0.157 / Cross valid method: THROUGHOUT / ESU R: 0.271 / ESU R Free: 0.207 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23585 1634 5 %RANDOM
Rwork0.19458 ---
obs0.19664 30848 97.22 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 60.404 Å2
Baniso -1Baniso -2Baniso -3
1--0.22 Å20 Å2-0.46 Å2
2--1.8 Å20 Å2
3----1.5 Å2
Refinement stepCycle: LAST / Resolution: 2.2→34.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4184 0 21 444 4649
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.024314
X-RAY DIFFRACTIONr_bond_other_d0.0020.023866
X-RAY DIFFRACTIONr_angle_refined_deg1.3221.9445871
X-RAY DIFFRACTIONr_angle_other_deg0.8343.0048933
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0365536
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.92324.439187
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.75315687
X-RAY DIFFRACTIONr_dihedral_angle_4_deg23.9481518
X-RAY DIFFRACTIONr_chiral_restr0.0980.2639
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0214922
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02996
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_it1.3273.1012153
X-RAY DIFFRACTIONr_mcbond_other1.3263.12152
X-RAY DIFFRACTIONr_mcangle_it2.0974.6452686
X-RAY DIFFRACTIONr_mcangle_other3.2977.4242687
X-RAY DIFFRACTIONr_scbond_it1.5383.2032161
X-RAY DIFFRACTIONr_scbond_other2.3025.0622162
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other3.6667.5233186
X-RAY DIFFRACTIONr_long_range_B_refined7.67452.35211915
X-RAY DIFFRACTIONr_long_range_B_other7.41852.19411704
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.201→2.258 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.32 113 -
Rwork0.308 1980 -
obs--84.29 %
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)
114.46998.3772-19.591910.6032-4.987933.5663-1.05390.59840.2801-0.56270.87210.71891.4189-0.28050.18190.33510.2312-0.1510.4589-0.01920.3855-17.619331.4799-37.9103
211.3585-8.6356-2.505415.44614.22161.6215-0.0482-0.32590.23120.34160.01470.516-0.3782-0.02610.03350.58130.16790.02290.399-0.01380.2608-8.528724.1459-38.1532
33.3907-1.37521.7437.7174-0.18676.79490.09260.403-0.2716-0.4071-0.2023-0.03610.19660.00210.10970.12430.05040.02430.245-0.00650.156-0.83945.1985-32.237
40.3799-1.9277-0.378610.95651.41272.03360.0220.0211-0.1053-0.47810.1491.1073-0.6594-0.6057-0.1710.45710.1794-0.09530.5055-0.01550.4177-10.907921.5142-34.8929
512.2865-8.59381.605922.1221-3.06683.79160.1566-0.45840.50990.798-0.0295-0.2429-0.1646-0.0455-0.12710.24590.10260.04590.2385-0.10330.2334-8.845130.1632-23.6379
69.364313.23896.669619.68715.525523.42310.1826-0.57570.8010.5574-0.5881.3671-0.7671-1.03850.40540.20210.22230.07350.3593-0.09470.4521-15.207720.0786-30.3027
720.794212.80252.406210.3865-6.169623.6585-0.50070.86060.6601-0.52490.5760.47840.54330.0382-0.07540.13920.1393-0.18640.3707-0.08930.4373-20.787611.8544-37.5225
821.20396.60883.93214.80051.63892.72940.1103-0.27310.00450.5608-0.23180.45550.2032-0.36320.12150.20090.04530.05290.2485-0.02520.1819-10.28589.1892-28.1293
97.49772.5961-3.102521.2999-7.32643.2480.2329-0.14930.2843-0.15-0.3152-0.3874-0.13190.18210.08220.39380.0419-0.02740.2548-0.04390.2601-3.316424.9837-31.1194
109.0947-7.4571-8.94086.30075.401631.5585-0.16490.00210.08430.1475-0.04850.06250.48940.98530.21340.5603-0.0207-0.06630.54760.00941.0895-0.207239.2344-32.6258
1111.5765-9.5057-21.009310.878215.676438.9390.1914-0.65530.5461-0.18580.4454-1.081-0.27421.2701-0.63690.0487-0.02610.02170.2620.04610.170423.133610.4223-20.1955
124.1039-1.5582-3.98492.31.74314.18880.4162-0.4570.4175-0.1092-0.0094-0.218-0.80880.6184-0.40670.5353-0.2746-0.03060.287-0.02080.082213.953114.7717-3.591
131.24780.14990.27041.4977-0.20912.0862-0.0882-0.09290.05480.10060.0883-0.0512-0.1842-0.0028-0.00010.07330.00480.0040.15660.00980.06969.02097.7213-16.3663
1410.09145.9473-5.8766.0087-4.12418.0496-0.14820.03070.11680.05020.1444-0.0462-0.352-0.14950.00380.0726-0.0043-0.01970.0877-0.01230.03366.060513.7269-12.0982
151.2806-0.0528-0.04391.37870.06093.4577-0.0136-0.007-0.02260.1058-0.0361-0.06430.0610.24450.04970.0506-0.005-0.01630.13350.00340.046412.52996.191-10.9807
166.9713-7.29090.901212.7904-1.77862.8141-0.2367-0.4392-0.31490.67010.0972-0.08530.25860.45190.13950.22250.1373-0.11780.4419-0.00920.146231.1447-4.341818.5832
172.9825-3.35232.34258.2741-1.99451.93370.10980.54980.1793-0.1196-0.2752-0.12460.06820.5030.16540.12180.0367-0.07760.38870.02630.136130.74741.90511.0978
180.7101-1.52591.41686.8789-0.34625.3306-0.09910.16270.10790.6503-0.1369-0.13610.29170.20380.23610.24480.0591-0.0940.30430.03170.169530.0277-5.19813.0452
1917.3458-18.565411.047322.1951-10.12988.4621-0.4045-0.04460.84960.58270.0689-1.1047-0.0790.21160.33560.1106-0.0078-0.04430.347-0.03040.339135.64035.071114.4421
204.96816.0585-8.603715.0197-4.619224.4545-0.1552-0.7884-0.31851.1851-0.6107-0.68380.50080.10630.76590.44220.3406-0.21730.79620.02880.348538.6263-4.98325.809
212.062-0.03172.04123.9836-2.1863.44340.2405-0.2094-0.46380.02660.17780.42090.4586-0.1495-0.41830.32880.10340.15330.1790.18150.441613.4871-16.9057-13.1562
2226.849-18.49850.172513.02371.10646.6463-0.32710.1338-0.02480.3383-0.04970.01220.91930.0760.37680.31790.03560.00890.1646-0.05050.265711.7779-18.0972-16.963
231.2951-0.5107-0.31662.1850.16332.3428-0.05840.204-0.2333-0.11860.051-0.17260.24120.28910.00730.12250.05440.01990.1658-0.0010.17115.8619-7.703-21.0169
2423.1648-8.2445-1.53979.65710.583615.08470.50670.0024-0.04790.4775-0.2202-0.15030.9569-0.2958-0.28650.2657-0.0566-0.00490.0428-0.09950.37913.8984-16.0028-24.8976
250.6027-0.12320.16730.24720.36851.6792-0.05520.0002-0.22330.18180.1093-0.04940.30870.2933-0.05410.21230.0859-0.01940.16370.04390.239619.2133-11.3011-3.9693
260.81252.51332.306411.68629.455913.80020.1106-0.382-0.23910.1478-0.68620.66590.2184-0.64580.57560.30170.1614-0.10380.40480.26640.606822.8718-14.440311.8893
270.6038-1.62390.02456.9878-1.12680.43840.34360.718-0.52230.2378-0.76020.6297-0.3171-0.45990.41660.77680.5673-0.07431.7977-0.89411.158313.7978-15.879322.7429
288.9571-5.187-10.32657.82739.38721.40890.0166-0.364-0.25160.2631-0.06110.33470.36040.59670.04450.11580.0538-0.0290.12420.03630.194722.7884-11.07138.632
294.86771.4791.26189.8237.52776.0472-0.2389-0.927-0.82271.6321-0.25751.26961.3982-0.08050.49630.89390.15280.13310.46070.20220.782419.4778-16.269623.0405
300.8975-5.6827-3.66838.312824.908316.21230.26910.1214-0.0259-0.5462-0.34320.1784-0.2781-0.16080.0740.7310.08270.03370.51290.01610.465125.4826-14.838732.8628
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1C120 - 127
2X-RAY DIFFRACTION2C128 - 136
3X-RAY DIFFRACTION3C137 - 154
4X-RAY DIFFRACTION4C155 - 166
5X-RAY DIFFRACTION5C167 - 178
6X-RAY DIFFRACTION6C179 - 187
7X-RAY DIFFRACTION7C188 - 196
8X-RAY DIFFRACTION8C197 - 208
9X-RAY DIFFRACTION9C209 - 221
10X-RAY DIFFRACTION10C222 - 226
11X-RAY DIFFRACTION11H1 - 5
12X-RAY DIFFRACTION12H6 - 23
13X-RAY DIFFRACTION13H24 - 61
14X-RAY DIFFRACTION14H62 - 83
15X-RAY DIFFRACTION15H84 - 119
16X-RAY DIFFRACTION16H120 - 145
17X-RAY DIFFRACTION17H146 - 165
18X-RAY DIFFRACTION18H166 - 195
19X-RAY DIFFRACTION19H196 - 213
20X-RAY DIFFRACTION20H214 - 218
21X-RAY DIFFRACTION21L1 - 18
22X-RAY DIFFRACTION22L19 - 24
23X-RAY DIFFRACTION23L25 - 65
24X-RAY DIFFRACTION24L66 - 70
25X-RAY DIFFRACTION25L71 - 127
26X-RAY DIFFRACTION26L128 - 145
27X-RAY DIFFRACTION27L146 - 156
28X-RAY DIFFRACTION28L157 - 180
29X-RAY DIFFRACTION29L181 - 208
30X-RAY DIFFRACTION30L209 - 213

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