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- PDB-6gk9: Inhibited structure of IMPDH from Pseudomonas aeruginosa -

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Open data


ID or keywords:

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Basic information

Entry
Database: PDB / ID: 6gk9
TitleInhibited structure of IMPDH from Pseudomonas aeruginosa
ComponentsInosine-5'-monophosphate dehydrogenase
KeywordsOXIDOREDUCTASE / IMP dehydrogenase / nucleotide biosynthesis / allosteric regulation
Function / homology
Function and homology information


IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / GTP biosynthetic process / ATP binding / identical protein binding / metal ion binding / cytoplasm
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-type TIM barrel
Similarity search - Domain/homology
Chem-F2K / Inosine-5'-monophosphate dehydrogenase
Similarity search - Component
Biological speciesPseudomonas aeruginosa PAO1 (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.54 Å
AuthorsLabesse, G. / Alexandre, T. / Haouz, A. / Munier-Lehmann, H.
CitationJournal: Eur J Med Chem / Year: 2019
Title: First-in-class allosteric inhibitors of bacterial IMPDHs.
Authors: Alexandre, T. / Lupan, A. / Helynck, O. / Vichier-Guerre, S. / Dugue, L. / Gelin, M. / Haouz, A. / Labesse, G. / Munier-Lehmann, H.
History
DepositionMay 18, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 27, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 17, 2024Group: Advisory / Data collection ...Advisory / Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_unobs_or_zero_occ_atoms
Item: _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: Inosine-5'-monophosphate dehydrogenase
B: Inosine-5'-monophosphate dehydrogenase
C: Inosine-5'-monophosphate dehydrogenase
D: Inosine-5'-monophosphate dehydrogenase
E: Inosine-5'-monophosphate dehydrogenase
F: Inosine-5'-monophosphate dehydrogenase
G: Inosine-5'-monophosphate dehydrogenase
H: Inosine-5'-monophosphate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)432,23911
Polymers431,5108
Non-polymers7293
Water17,691982
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: SAXS, scanning transmission electron microscopy, mass spectrometry, gel filtration, equilibrium centrifugation
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area31950 Å2
ΔGint-191 kcal/mol
Surface area124620 Å2
MethodPISA
Unit cell
Length a, b, c (Å)115.640, 196.958, 123.628
Angle α, β, γ (deg.)90.000, 113.990, 90.000
Int Tables number4
Space group name H-MP1211

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Components

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


Mass: 53938.699 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Pseudomonas aeruginosa PAO1 (bacteria) / Gene: guaB, PA3770 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9HXM5, IMP dehydrogenase
#2: Chemical ChemComp-F2K / (5~{S})-7-azanyl-5-(4-chlorophenyl)-2,4-bis(oxidanylidene)-1,5-dihydropyrano[2,3-d]pyrimidine-6-carbonitrile


Mass: 316.699 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H9ClN4O3
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 982 / 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: 58.74 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: Protein concentration: 7.8 mg.mL-1 lithium chloride 500 mM, ammonium sulphate 50 mM, PEG8000 8%

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.98011 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 7, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98011 Å / Relative weight: 1
ReflectionResolution: 2.54→48.99 Å / Num. all: 165995 / Num. obs: 165995 / % possible obs: 100 % / Redundancy: 4.7 % / Biso Wilson estimate: 43.37 Å2 / Rpim(I) all: 0.069 / Rrim(I) all: 0.153 / Rsym value: 0.121 / Net I/av σ(I): 4.1 / Net I/σ(I): 7.6 / Num. measured all: 778371
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
2.54-2.684.70.5081.4242400.2790.6290.508100
2.68-2.844.60.3352.1228640.1870.4180.335100
2.84-3.044.70.2452.9215330.1370.3050.245100
3.04-3.284.70.1714200200.0950.2130.171100
3.28-3.594.70.1245.2184370.070.1560.124100
3.59-4.024.70.1055.8166870.060.1320.105100
4.02-4.644.70.0916.5147410.0530.1150.091100
4.64-5.684.70.096.4124590.0510.1130.09100
5.68-8.034.70.0896.396630.0510.1120.089100
8.03-48.994.60.0895.153510.0530.1130.08999.5

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Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 35.41 / Model details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2.54 Å48.99 Å
Translation2.54 Å48.99 Å

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Processing

Software
NameVersionClassificationNB
XDSdata reduction
SCALA3.3.15data scaling
PHASER2.1.4phasing
PHENIXrefinement
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4dqw
Resolution: 2.54→48.99 Å / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 19.39
RfactorNum. reflection% reflection
Rfree0.2054 8272 4.99 %
Rwork0.1593 --
obs0.1616 165931 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 187.4 Å2 / Biso mean: 53.6059 Å2 / Biso min: 18.66 Å2
Refinement stepCycle: final / Resolution: 2.54→48.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms23216 0 67 982 24265
Biso mean--95.1 52.48 -
Num. residues----3142
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
2.54-2.56890.26932660.216353045570
2.5689-2.59910.26542730.20351865459
2.5991-2.63080.25012970.196352715568
2.6308-2.66410.24982330.184752455478
2.6641-2.69910.25052720.1852505522
2.6991-2.73610.24992690.179152515520
2.7361-2.77520.22932840.170152215505
2.7752-2.81660.2292690.168952775546
2.8166-2.86060.22212980.17151855483
2.8606-2.90750.2312700.182552725542
2.9075-2.95760.27922680.188752535521
2.9576-3.01140.22972600.197652285488
3.0114-3.06930.23262690.183252645533
3.0693-3.1320.2432890.175652695558
3.132-3.20010.23112710.177652365507
3.2001-3.27450.22852780.168852305508
3.2745-3.35640.2142620.165752565518
3.3564-3.44710.21662700.167952625532
3.4471-3.54850.19882670.168152485515
3.5485-3.6630.20932720.157552415513
3.663-3.79390.18482630.149652805543
3.7939-3.94570.19912910.145452625553
3.9457-4.12520.16842980.137752345532
4.1252-4.34250.18672880.127552395527
4.3425-4.61440.17532930.124952715564
4.6144-4.97040.1592750.123952395514
4.9704-5.470.18973000.143752725572
5.47-6.26010.19732760.155552815557
6.2601-7.88180.19632750.155652875562
7.8818-48.99860.20182760.181553455621
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)
10.9232-0.26020.24540.4053-0.52351.27080.0376-0.2552-0.0160.0603-0.067-0.03580.0450.20570.06660.2522-0.0036-0.00690.3001-0.00470.261458.2990.820111.3243
22.14740.611-1.45962.0302-1.55484.12480.1032-0.09810.03330.05970.17480.1234-0.3992-0.3953-0.26310.5351-0.01010.04470.8223-0.00530.384486.7434-4.857330.9607
31.89830.4002-0.20571.1173-0.25781.0455-0.0246-0.2526-0.08560.087-0.0232-0.1257-0.00150.02710.03430.2470.0033-0.01690.2861-0.01840.21751.07451.8078.4927
41.25730.64020.11180.9280.28050.44460.1017-0.23810.06460.015-0.088-0.0866-0.06460.1045-0.00890.2126-0.03240.01880.2834-0.00470.309187.4219-25.4598-10.1267
52.3139-1.2663-1.23823.27061.11611.77580.0067-0.32390.2479-0.3540.3065-0.3318-0.32410.4276-0.28020.3702-0.08240.07350.8019-0.08170.4492105.2459-3.157718.2782
60.52510.11230.86070.38380.94672.4001-0.0592-0.30220.08870.1884-0.04310.15090.2139-0.00480.14990.3511-0.06140.07360.6044-0.0190.468997.7874-19.954510.6571
71.22290.3828-0.00320.8905-0.07281.48390.02930.06030.0227-0.0306-0.0087-0.082-0.07680.006-0.02430.21620.00960.03270.2442-0.01380.32184.1776-28.9631-19.1727
81.14730.03670.43621.25450.31860.87260.0927-0.259-0.34620.0909-0.06340.14780.186-0.113-0.02010.251-0.02930.02880.31410.07910.351214.9913-20.84560.1472
92.49740.1485-0.1293.20430.73762.76420.02740.59080.01250.3880.31161.1711-0.7806-0.5012-0.26670.9910.05050.31930.98820.06221.26983.7139-50.333218.716
100.32870.5616-0.5742.19-2.25932.4311-0.333-0.2558-0.7630.6680.1173-0.03360.7572-0.26210.18070.8679-0.01830.16030.58890.26090.805710.1386-35.866415.1075
111.1196-0.11940.64750.66720.16091.44960.0511-0.0362-0.19540.0374-0.05810.07610.0975-0.02930.0180.2259-0.00380.04410.31070.03520.345315.3451-14.8808-5.5
125.19723.2114-2.12644.0329-1.73731.92050.06690.0042-0.19280.3427-0.0517-0.1493-0.3285-0.11280.02530.28040.0294-0.02170.3034-0.00420.280420.02025.1235-23.2248
130.46440.0970.7050.58130.50342.3957-0.16140.39350.032-0.34470.21520.13230.0124-0.1087-0.06460.3992-0.0868-0.04760.44530.01790.284515.2813-5.9382-52.389
141.8263-0.6191-0.54472.8193-0.0082.15530.11640.3554-0.0492-0.43550.07180.23490.078-0.149-0.13410.558-0.0755-0.20720.850.17130.52481.7583-21.5803-78.1088
150.820.84991.11052.23571.39922.0923-0.10850.09090.1576-0.26710.00990.3358-0.1222-0.1970.10290.493-0.049-0.09370.57680.09090.331711.438-2.3733-59.0186
163.73111.6738-0.00061.21250.96341.968-0.18630.14990.1324-0.10910.10480.1317-0.121-0.13130.01780.4534-0.0044-0.0460.27890.06580.314923.780110.6016-41.9897
170.41760.37870.16481.83550.56351.48720.03650.0234-0.0585-0.1098-0.0268-0.1075-0.0184-0.0068-0.01840.2485-0.0109-0.02080.3080.04640.257119.7942-5.1842-36.1055
180.94650.0217-0.21131.1468-0.04441.1061-0.0122-0.0555-0.06990.12020.07070.1760.0372-0.2466-0.04980.29920.0138-0.03380.18950.01770.43345.319-53.3452-2.173
192.7296-0.2763-2.02812.2753-0.18843.0943-0.1676-0.4415-0.09190.830.15690.76-0.1449-0.07690.06010.65770.07660.1240.5954-0.0080.759222.0119-57.840620.6295
201.42970.25240.23720.8571-0.06471.1688-0.06830.05550.0420.01430.07980.0859-0.0045-0.0374-0.01960.2860.01830.00030.17010.01850.389552.8805-52.1947-7.0148
211.6437-0.54012.22781.02190.20316.45770.20730.0004-0.065-0.14030.29440.140.2043-0.2226-0.48110.2633-0.071-0.00060.28810.06160.287737.074616.3136-25.033
222.3308-0.23170.46011.4230.21011.1568-0.13270.460.0674-0.42340.1657-0.308-0.13920.4189-0.0230.4787-0.11450.14040.4483-0.01470.345163.829420.5508-38.5362
232.4497-0.743-1.54221.90820.16124.368-0.25480.33320.1887-0.13130.3103-0.4157-0.18730.4938-0.05990.3547-0.10590.08050.3718-0.02830.461168.981624.5388-24.7653
241.9462-0.242-0.04220.1837-0.59922.3118-0.08430.1230.0004-0.17010.0841-0.1807-0.03020.155-0.01850.3465-0.04830.04830.2445-0.04560.374358.595424.3572-20.017
252.2937-0.2099-0.22090.05260.09621.69370.07010.25920.0885-0.00460.0625-0.23290.2374-0.1211-0.12120.3858-0.05580.01010.245-0.00560.2850.75717.2381-30.2097
262.2198-0.5936-0.40831.82570.87962.21690.00950.1508-0.1072-0.44340.2355-0.13850.3950.1073-0.2470.4825-0.08750.01210.2974-0.01540.285850.09059.2688-37.2585
274.84671.78292.13882.16931.27592.28280.0191-0.1323-0.0596-0.3836-0.0571-0.07460.09740.06510.05140.41080.02410.01180.4030.00540.275873.5054-37.399-42.6394
281.12280.13020.0961.5407-0.31991.54060.02860.41070.1744-0.5111-0.0524-0.0857-0.16570.27230.02320.6098-0.04350.07040.452-0.01670.297472.2061-17.0327-58.4572
290.5929-0.954-0.5182.4303-0.11631.37180.33980.25930.5224-0.4868-0.021-0.5219-0.4950.0031-0.25750.8975-0.0850.06370.48610.10060.585572.8114-3.1608-65.3344
301.1509-0.08150.07383.2368-0.20672.1355-0.02220.55850.1805-1.0523-0.04570.1837-0.01760.14010.03610.8318-0.03040.0290.6596-0.00630.293866.8082-20.5377-69.5867
312.47580.69640.12081.897-1.08690.80170.10950.2893-0.0227-0.5459-0.11090.1283-0.21060.2544-0.00390.6859-0.00290.01340.5032-0.12380.279264.4058-32.8107-63.7211
321.38040.41810.88382.0962-0.13040.93720.0505-0.03350.1517-0.1461-0.13990.0646-0.1350.00180.08520.4631-0.02410.08440.4238-0.06740.307370.9069-22.2473-48.1949
331.46530.0033-0.06740.7979-0.41390.3435-0.05710.2186-0.0182-0.26370.21990.33690.2016-0.3037-0.13190.5457-0.0689-0.18010.5467-0.0030.486530.109-46.2447-50.8585
343.3297-1.754-0.82112.66080.30171.5320.1705-0.4865-1.4755-0.05270.00971.18260.5962-0.6532-0.15530.9672-0.3223-0.31011.00090.25141.1505-5.2867-41.8012-67.0666
353.1874-0.98842.25760.3374-0.68151.60110.26790.0112-0.24-0.30240.05560.41620.45470.1345-0.32520.8419-0.0718-0.27840.6970.07780.830713.601-40.1064-70.3162
361.1968-0.0464-0.08981.2345-0.59361.68240.06910.1586-0.2386-0.26850.14480.28510.1625-0.1873-0.18610.4444-0.0594-0.14390.3401-0.04660.405336.7346-49.137-45.004
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 0 through 105 )A0 - 105
2X-RAY DIFFRACTION2chain 'A' and (resid 106 through 202 )A106 - 202
3X-RAY DIFFRACTION3chain 'A' and (resid 203 through 467 )A203 - 467
4X-RAY DIFFRACTION4chain 'B' and (resid 1 through 105 )B1 - 105
5X-RAY DIFFRACTION5chain 'B' and (resid 106 through 166 )B106 - 166
6X-RAY DIFFRACTION6chain 'B' and (resid 167 through 223 )B167 - 223
7X-RAY DIFFRACTION7chain 'B' and (resid 224 through 466 )B224 - 466
8X-RAY DIFFRACTION8chain 'C' and (resid 1 through 107 )C1 - 107
9X-RAY DIFFRACTION9chain 'C' and (resid 108 through 177 )C108 - 177
10X-RAY DIFFRACTION10chain 'C' and (resid 178 through 219 )C178 - 219
11X-RAY DIFFRACTION11chain 'C' and (resid 220 through 467 )C220 - 467
12X-RAY DIFFRACTION12chain 'D' and (resid 1 through 24 )D1 - 24
13X-RAY DIFFRACTION13chain 'D' and (resid 25 through 98 )D25 - 98
14X-RAY DIFFRACTION14chain 'D' and (resid 99 through 176 )D99 - 176
15X-RAY DIFFRACTION15chain 'D' and (resid 177 through 266 )D177 - 266
16X-RAY DIFFRACTION16chain 'D' and (resid 267 through 315 )D267 - 315
17X-RAY DIFFRACTION17chain 'D' and (resid 316 through 466 )D316 - 466
18X-RAY DIFFRACTION18chain 'E' and (resid 1 through 105 )E1 - 105
19X-RAY DIFFRACTION19chain 'E' and (resid 106 through 210 )E106 - 210
20X-RAY DIFFRACTION20chain 'E' and (resid 211 through 467 )E211 - 467
21X-RAY DIFFRACTION21chain 'F' and (resid 1 through 24 )F1 - 24
22X-RAY DIFFRACTION22chain 'F' and (resid 25 through 226 )F25 - 226
23X-RAY DIFFRACTION23chain 'F' and (resid 227 through 253 )F227 - 253
24X-RAY DIFFRACTION24chain 'F' and (resid 254 through 315 )F254 - 315
25X-RAY DIFFRACTION25chain 'F' and (resid 316 through 371 )F316 - 371
26X-RAY DIFFRACTION26chain 'F' and (resid 372 through 466 )F372 - 466
27X-RAY DIFFRACTION27chain 'G' and (resid 1 through 24 )G1 - 24
28X-RAY DIFFRACTION28chain 'G' and (resid 25 through 75 )G25 - 75
29X-RAY DIFFRACTION29chain 'G' and (resid 76 through 208 )G76 - 208
30X-RAY DIFFRACTION30chain 'G' and (resid 209 through 253 )G209 - 253
31X-RAY DIFFRACTION31chain 'G' and (resid 254 through 315 )G254 - 315
32X-RAY DIFFRACTION32chain 'G' and (resid 316 through 466 )G316 - 466
33X-RAY DIFFRACTION33chain 'H' and (resid 1 through 105 )H1 - 105
34X-RAY DIFFRACTION34chain 'H' and (resid 106 through 166 )H106 - 166
35X-RAY DIFFRACTION35chain 'H' and (resid 167 through 212 )H167 - 212
36X-RAY DIFFRACTION36chain 'H' and (resid 213 through 467 )H213 - 467

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Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

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Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

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