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- PDB-4mz8: Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase, ... -

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Basic information

Entry
Database: PDB / ID: 4mz8
TitleCrystal Structure of the Inosine 5'-monophosphate Dehydrogenase, with an Internal Deletion of CBS Domain from Campylobacter jejuni complexed with inhibitor compound C91
ComponentsInosine-5'-monophosphate dehydrogenase
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / Structural Genomics / NIAID / National Institute of Allergy and Infectious Diseases / Center for Structural Genomics of Infectious Diseases / CSGID / TIM barrel / alpha-beta structure / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / nucleotide binding / metal ion binding
Similarity search - Function
IMP dehydrogenase / GMP reductase domain / Inosine-5'-monophosphate dehydrogenase / IMP dehydrogenase / GMP reductase, conserved site / IMP dehydrogenase / GMP reductase signature. / IMP dehydrogenase/GMP reductase / IMP dehydrogenase / GMP reductase domain / CBS domain superfamily / Domain in cystathionine beta-synthase and other proteins. / CBS domain / CBS domain ...IMP dehydrogenase / GMP reductase domain / Inosine-5'-monophosphate dehydrogenase / IMP dehydrogenase / GMP reductase, conserved site / IMP dehydrogenase / GMP reductase signature. / IMP dehydrogenase/GMP reductase / IMP dehydrogenase / GMP reductase domain / CBS domain superfamily / Domain in cystathionine beta-synthase and other proteins. / CBS domain / CBS domain / CBS domain profile. / Aldolase class I / Aldolase-type TIM barrel / TIM Barrel / Alpha-Beta Barrel / Alpha Beta
Similarity search - Domain/homology
dimethyl ether / ACETIC ACID / Chem-C91 / FORMIC ACID / INOSINIC ACID / Inosine-5'-monophosphate dehydrogenase
Similarity search - Component
Biological speciesCampylobacter jejuni subsp. jejuni (Campylobacter)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5004 Å
AuthorsKim, Y. / Makowska-Grzyska, M. / Gu, M. / Gorla, S.K. / Hedstrom, L. / Anderson, W.F. / Joachimiak, A. / CSGID / Center for Structural Genomics of Infectious Diseases (CSGID)
CitationJournal: To be Published
Title: Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase, with a Internal Deletion of CBS Domain from Campylobacter jejuni complexed with inhibitor compound C91
Authors: Kim, Y. / Makowska-Grzyska, M. / Gu, M. / Anderson, W.F. / Joachimiak, A.
History
DepositionSep 29, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 16, 2014Provider: repository / Type: Initial release
Revision 1.1May 17, 2017Group: Structure summary
Revision 1.2Jan 24, 2018Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 1.3Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Inosine-5'-monophosphate dehydrogenase
B: Inosine-5'-monophosphate dehydrogenase
C: Inosine-5'-monophosphate dehydrogenase
D: Inosine-5'-monophosphate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)178,57235
Polymers174,0994
Non-polymers4,47331
Water5,296294
1
A: Inosine-5'-monophosphate dehydrogenase
B: Inosine-5'-monophosphate dehydrogenase
hetero molecules

A: Inosine-5'-monophosphate dehydrogenase
B: Inosine-5'-monophosphate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)179,16544
Polymers174,0994
Non-polymers5,06640
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_554x-y,-y,-z-1/31
Buried area18240 Å2
ΔGint-103 kcal/mol
Surface area50040 Å2
MethodPISA
2
C: Inosine-5'-monophosphate dehydrogenase
D: Inosine-5'-monophosphate dehydrogenase
hetero molecules

C: Inosine-5'-monophosphate dehydrogenase
D: Inosine-5'-monophosphate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)177,97926
Polymers174,0994
Non-polymers3,88022
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_554x-y,-y,-z-1/31
Buried area16680 Å2
ΔGint-88 kcal/mol
Surface area50040 Å2
MethodPISA
Unit cell
Length a, b, c (Å)114.460, 114.460, 256.314
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121
Components on special symmetry positions
IDModelComponents
11A-508-

CL

21B-710-

HOH

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Components

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Protein , 1 types, 4 molecules ABCD

#1: Protein
Inosine-5'-monophosphate dehydrogenase / IMP dehydrogenase / IMPD / IMPDH


Mass: 43524.820 Da / Num. of mol.: 4 / Fragment: IMPDH-delta-S-CBS / Mutation: CBS domain (residues 92-195) is replaced with G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Campylobacter jejuni subsp. jejuni (Campylobacter)
Strain: NCTC 11168 / Gene: guaB, Cj1058c / Plasmid: pMCSG7 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 magic / References: UniProt: Q0P9J4, IMP dehydrogenase

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Non-polymers , 10 types, 325 molecules

#2: Chemical
ChemComp-IMP / INOSINIC ACID / Inosinic acid


Mass: 348.206 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H13N4O8P
#3: Chemical
ChemComp-C91 / N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide


Mass: 378.426 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H18N4O
#4: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-FMT / FORMIC ACID / Formic acid


Mass: 46.025 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: CH2O2
#7: Chemical ChemComp-ACY / ACETIC ACID / Acetic acid


Mass: 60.052 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H4O2
#8: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#9: Chemical
ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Cl
#10: Chemical ChemComp-2F2 / dimethyl ether / Dimethyl ether


Mass: 46.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O
#11: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 294 / 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: 2.95 Å3/Da / Density % sol: 58.33 %
Crystal growTemperature: 289 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 1.6 M ammonium sulfate, 0.1 M MES pH 6.5, 10 % dioxane, VAPOR DIFFUSION, SITTING DROP, temperature 100K, temperature 289K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97926 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 20, 2012 / Details: mirrors
RadiationMonochromator: double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97926 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. all: 68101 / Num. obs: 68101 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 8.8 % / Biso Wilson estimate: 46.46 Å2 / Rsym value: 0.109 / Net I/σ(I): 10.2
Reflection shellResolution: 2.5→2.54 Å / Redundancy: 6.2 % / Mean I/σ(I) obs: 3 / Rsym value: 0.699 / % possible all: 99

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Processing

Software
NameVersionClassification
SBC-Collectdata collection
HKL-3000data collection
HKL-3000phasing
MOLREPphasing
PHENIX(phenix.refine: dev_1367)refinement
HKL-3000data reduction
HKL-3000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4FO4
Resolution: 2.5004→39.231 Å / SU ML: 0.28 / Isotropic thermal model: mixed / σ(F): 1.33 / Phase error: 23.01 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2167 3446 5.08 %
Rwork0.1756 --
obs0.1777 67873 99.68 %
all-67873 -
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 65.9 Å2
Refinement stepCycle: LAST / Resolution: 2.5004→39.231 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10444 0 296 294 11034
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00811031
X-RAY DIFFRACTIONf_angle_d1.1414898
X-RAY DIFFRACTIONf_dihedral_angle_d15.4384096
X-RAY DIFFRACTIONf_chiral_restr0.0681716
X-RAY DIFFRACTIONf_plane_restr0.0041891
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.5004-2.53460.31541450.25022481X-RAY DIFFRACTION97
2.5346-2.57080.26071100.23932537X-RAY DIFFRACTION99
2.5708-2.60920.25531380.22032574X-RAY DIFFRACTION100
2.6092-2.64990.27081500.21362484X-RAY DIFFRACTION100
2.6499-2.69340.27751380.22072528X-RAY DIFFRACTION100
2.6934-2.73980.25151340.22922553X-RAY DIFFRACTION100
2.7398-2.78960.28911460.20822594X-RAY DIFFRACTION100
2.7896-2.84320.25361290.21122530X-RAY DIFFRACTION100
2.8432-2.90130.26711360.21072532X-RAY DIFFRACTION100
2.9013-2.96430.23921180.19942599X-RAY DIFFRACTION100
2.9643-3.03330.26271600.20632535X-RAY DIFFRACTION100
3.0333-3.10910.25761320.21062550X-RAY DIFFRACTION100
3.1091-3.19310.27161270.20172592X-RAY DIFFRACTION100
3.1931-3.2870.25581500.18752539X-RAY DIFFRACTION100
3.287-3.39310.22841400.18712561X-RAY DIFFRACTION100
3.3931-3.51430.25071300.17972577X-RAY DIFFRACTION100
3.5143-3.65490.22331330.17292584X-RAY DIFFRACTION100
3.6549-3.82110.23211240.15872619X-RAY DIFFRACTION100
3.8211-4.02230.20851270.15042554X-RAY DIFFRACTION100
4.0223-4.27410.15821390.14212604X-RAY DIFFRACTION100
4.2741-4.60360.17431510.13562618X-RAY DIFFRACTION100
4.6036-5.0660.17221530.13612586X-RAY DIFFRACTION100
5.066-5.79710.17271430.16022643X-RAY DIFFRACTION100
5.7971-7.2960.20581320.17932676X-RAY DIFFRACTION100
7.296-39.23580.19481610.17532777X-RAY DIFFRACTION99
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)
11.63160.1592-0.83341.1761-0.23183.03160.0851-0.1452-0.2270.2804-0.1708-0.0110.22040.18860.11480.48350.028-0.03040.29270.06870.277865.9843-22.4843-20.8837
22.1958-0.7079-0.88855.82910.944.39790.0307-0.3686-0.5190.8487-0.0565-0.09240.93850.0130.06710.6622-0.0579-0.05590.44510.17320.418463.8819-28.5308-7.8695
30.93980.04-0.11.1120.21690.60570.0939-0.1978-0.13770.2563-0.1373-0.24840.02560.25540.04630.4624-0.007-0.06390.38660.09680.271173.2805-14.1541-17.4754
43.15561.21611.23672.94440.6761.92290.0382-0.5378-0.08310.3513-0.13650.1343-0.1693-0.31660.08710.4213-0.02640.05510.34050.00820.29350.3757-10.9199-20.9131
57.3441-2.2753-3.21291.5971.71753.96320.0536-0.0691-0.6695-0.0399-0.1668-0.03310.51880.08590.12430.50610.0171-0.03170.29720.06410.336464.056-28.3631-33.0378
63.05290.51831.61511.8027-0.27852.0820.01930.0268-0.09190.0022-0.07390.01080.07420.13790.0660.50150.07050.07960.42130.03920.258367.091-19.0182-40.4866
71.3709-0.94370.18812.57560.24721.1325-0.0126-0.14730.20560.3476-0.0455-0.2144-0.2980.1530.04620.5406-0.1684-0.07180.3582-0.00040.288765.970721.5693-20.482
82.3928-1.36410.83123.47510.3655.5631-0.1436-0.48380.29470.6881-0.05890.1084-0.5831-0.04540.14650.7137-0.1348-0.05320.4062-0.09570.365363.626234.7522-14.1729
91.0219-0.15970.04760.7981-0.00611.08060.0303-0.15320.15460.2244-0.0741-0.1675-0.29640.23410.02930.495-0.1442-0.05190.30090.00880.274468.504824.2195-28.2596
101.3004-0.3638-0.10211.5362-0.21371.4821-0.0534-0.12520.01590.2179-0.0655-0.0959-0.09850.16640.14450.4422-0.1484-0.05720.34970.00170.275364.657913.1848-24.9877
118.12092.1792-1.86633.32092.61014.62630.12510.38290.5645-0.3949-0.07330.3022-0.8172-0.3301-0.05170.60130.0083-0.0130.34820.0620.28854.3196-0.7846-25.6911
121.29060.2046-0.10981.0067-0.4011.27250.0722-0.0231-0.0275-0.02990.45770.88360.3719-0.3922-0.31470.6247-0.1856-0.0240.52020.29461.11419.0665-31.3565-35.19
131.01420.654-0.65832.45110.43412.2182-0.18350.0643-0.4386-0.36040.22330.46020.7211-0.2475-0.0841.0035-0.2791-0.24530.60170.27411.194320.5816-45.0227-38.7234
140.01920.0669-0.05370.136-0.14080.14190.1103-0.0067-0.2125-0.41150.52061.27920.5592-0.68060.01540.7468-0.3945-0.43210.69350.48371.685211.2131-28.8868-44.9601
152.752-0.76081.0521.6926-0.60692.8001-0.03410.1633-0.0847-0.58450.17010.58930.5943-0.0891-0.17050.5134-0.1119-0.07740.36740.06540.469234.9843-24.0018-44.6786
165.06330.1498-3.07370.97131.21763.63420.0815-0.5453-0.16860.51370.33720.7455-0.1291-0.3233-0.15270.5438-0.0220.25050.62810.35720.986820.3231-23.863-24.5773
174.21762.0199-0.10541.531-0.26941.41920.1656-0.1398-0.02280.41790.31261.22-0.0153-0.4597-0.39650.54020.0780.24880.58050.2641.161317.2819-12.545-28.3253
181.8633-0.58010.13020.9410.11480.90290.12150.0442-0.38660.13750.12650.5893-0.199-0.1901-0.00070.79520.27620.63130.760.34661.58687.79019.6946-29.6255
190.8701-1.1194-0.30951.86650.19060.4940.0606-0.14840.20570.43510.20850.5155-0.3718-0.2244-0.06141.5140.41990.85460.78940.08980.993719.42439.8971-8.775
200.36920.125-0.18110.4658-0.58420.73470.0556-0.36030.15390.53730.08830.1405-0.43960.2326-0.19511.80630.27070.73690.89710.13890.755926.8233-0.3037-0.3707
210.9281-0.0189-0.7081.40080.90261.98180.1355-0.2510.13730.307-0.0860.2104-0.4725-0.0805-0.25231.86440.41720.88060.98610.23131.051719.48332.34851.9601
220.84130.2037-0.44090.0426-0.10820.22630.1969-0.55520.09020.67390.03180.6128-0.1206-0.33690.08491.25160.2780.97351.04050.43271.34429.958-6.4703-8.6766
230.0091-0.0295-0.03380.06630.08530.08160.0935-0.2965-0.25550.66640.37031.1643-0.309-0.499-0.07280.86120.29710.64620.79190.35061.501412.07031.9148-20.3411
243.6809-1.5151-0.181.99231.15120.90450.0492-0.35320.21461.06670.32810.5225-0.5166-0.363-0.28290.95060.13560.35550.50610.10130.562630.06123.6756-18.714
252.29030.0601-1.41110.41690.59131.86680.114-0.1327-0.09090.65780.37880.9686-0.344-0.5357-0.37410.81950.2870.37180.68930.37181.17817.223814.509-30.5015
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 86 )
2X-RAY DIFFRACTION2chain 'A' and (resid 87 through 236 )
3X-RAY DIFFRACTION3chain 'A' and (resid 237 through 361 )
4X-RAY DIFFRACTION4chain 'A' and (resid 362 through 422 )
5X-RAY DIFFRACTION5chain 'A' and (resid 423 through 441 )
6X-RAY DIFFRACTION6chain 'A' and (resid 442 through 482 )
7X-RAY DIFFRACTION7chain 'B' and (resid 1 through 86 )
8X-RAY DIFFRACTION8chain 'B' and (resid 87 through 235 )
9X-RAY DIFFRACTION9chain 'B' and (resid 236 through 382 )
10X-RAY DIFFRACTION10chain 'B' and (resid 383 through 466 )
11X-RAY DIFFRACTION11chain 'B' and (resid 467 through 483 )
12X-RAY DIFFRACTION12chain 'C' and (resid 5 through 86 )
13X-RAY DIFFRACTION13chain 'C' and (resid 87 through 236 )
14X-RAY DIFFRACTION14chain 'C' and (resid 237 through 361 )
15X-RAY DIFFRACTION15chain 'C' and (resid 362 through 422 )
16X-RAY DIFFRACTION16chain 'C' and (resid 423 through 441 )
17X-RAY DIFFRACTION17chain 'C' and (resid 442 through 482 )
18X-RAY DIFFRACTION18chain 'D' and (resid 2 through 23 )
19X-RAY DIFFRACTION19chain 'D' and (resid 24 through 62 )
20X-RAY DIFFRACTION20chain 'D' and (resid 63 through 87 )
21X-RAY DIFFRACTION21chain 'D' and (resid 88 through 236 )
22X-RAY DIFFRACTION22chain 'D' and (resid 237 through 302 )
23X-RAY DIFFRACTION23chain 'D' and (resid 303 through 361 )
24X-RAY DIFFRACTION24chain 'D' and (resid 362 through 441 )
25X-RAY DIFFRACTION25chain 'D' and (resid 442 through 482 )

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