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- PDB-8tbu: Structure of human erythrocyte pyruvate kinase in complex with an... -

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ID or keywords:

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Basic information

Entry
Database: PDB / ID: 8tbu
TitleStructure of human erythrocyte pyruvate kinase in complex with an allosteric activator Compound 12
ComponentsPyruvate kinase PKLR
KeywordsTRANSFERASE/ACTIVATOR / Erythrocyte pyruvate kinase / PKR / PKLR / Allosteric Activator / Glycolysis / TRANSFERASE / TRANSFERASE-ACTIVATOR complex
Function / homology
Function and homology information


pyruvate kinase complex / pyruvate biosynthetic process / SARS-CoV-1-host interactions / ChREBP activates metabolic gene expression / pyruvate kinase / pyruvate kinase activity / Pyruvate metabolism / monosaccharide binding / response to metal ion / Glycolysis ...pyruvate kinase complex / pyruvate biosynthetic process / SARS-CoV-1-host interactions / ChREBP activates metabolic gene expression / pyruvate kinase / pyruvate kinase activity / Pyruvate metabolism / monosaccharide binding / response to metal ion / Glycolysis / response to ATP / Regulation of gene expression in beta cells / potassium ion binding / response to glucose / response to cAMP / cellular response to epinephrine stimulus / response to nutrient / glycolytic process / cellular response to insulin stimulus / kinase activity / response to hypoxia / magnesium ion binding / extracellular exosome / ATP binding / cytosol / cytoplasm
Similarity search - Function
Pyruvate kinase, active site / Pyruvate kinase active site signature. / Pyruvate kinase / Pyruvate kinase, barrel / Pyruvate kinase, insert domain superfamily / Pyruvate kinase, barrel domain / Pyruvate kinase, C-terminal / Pyruvate kinase, C-terminal domain superfamily / Pyruvate kinase, alpha/beta domain / Pyruvate kinase-like, insert domain superfamily ...Pyruvate kinase, active site / Pyruvate kinase active site signature. / Pyruvate kinase / Pyruvate kinase, barrel / Pyruvate kinase, insert domain superfamily / Pyruvate kinase, barrel domain / Pyruvate kinase, C-terminal / Pyruvate kinase, C-terminal domain superfamily / Pyruvate kinase, alpha/beta domain / Pyruvate kinase-like, insert domain superfamily / Pyruvate kinase-like domain superfamily / Pyruvate/Phosphoenolpyruvate kinase-like domain superfamily
Similarity search - Domain/homology
1,6-di-O-phosphono-beta-D-fructofuranose / Chem-I0R / : / : / PYRUVIC ACID / Pyruvate kinase PKLR
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 Å
AuthorsJin, L. / Padyana, A.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Chemmedchem / Year: 2024
Title: Structure-Based Design of AG-946, a Pyruvate Kinase Activator.
Authors: Liu, T. / Padyana, A.K. / Judd, E.T. / Jin, L. / Hammoudeh, D. / Kung, C. / Dang, L.
History
DepositionJun 29, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 27, 2023Provider: repository / Type: Initial release
Revision 1.1Mar 20, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.year / _citation_author.identifier_ORCID

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Pyruvate kinase PKLR
B: Pyruvate kinase PKLR
C: Pyruvate kinase PKLR
D: Pyruvate kinase PKLR
E: Pyruvate kinase PKLR
F: Pyruvate kinase PKLR
G: Pyruvate kinase PKLR
H: Pyruvate kinase PKLR
hetero molecules


Theoretical massNumber of molelcules
Total (without water)474,39436
Polymers469,3218
Non-polymers5,07228
Water27,8151544
1
A: Pyruvate kinase PKLR
B: Pyruvate kinase PKLR
C: Pyruvate kinase PKLR
D: Pyruvate kinase PKLR
hetero molecules


Theoretical massNumber of molelcules
Total (without water)237,23619
Polymers234,6614
Non-polymers2,57515
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area22220 Å2
ΔGint-112 kcal/mol
Surface area66920 Å2
MethodPISA
2
E: Pyruvate kinase PKLR
F: Pyruvate kinase PKLR
G: Pyruvate kinase PKLR
H: Pyruvate kinase PKLR
hetero molecules


Theoretical massNumber of molelcules
Total (without water)237,15817
Polymers234,6614
Non-polymers2,49713
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area21350 Å2
ΔGint-113 kcal/mol
Surface area64140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)110.323, 122.845, 378.582
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

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Protein / Sugars , 2 types, 16 molecules ABCDEFGH

#1: Protein
Pyruvate kinase PKLR / Pyruvate kinase 1 / Pyruvate kinase isozymes L/R / R-type/L-type pyruvate kinase / Red cell/liver ...Pyruvate kinase 1 / Pyruvate kinase isozymes L/R / R-type/L-type pyruvate kinase / Red cell/liver pyruvate kinase


Mass: 58665.176 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Details: Red blood cell/liver isoform / Source: (gene. exp.) Homo sapiens (human) / Gene: PKLR, PK1, PKL / Production host: Escherichia coli (E. coli) / References: UniProt: P30613, pyruvate kinase
#4: Sugar
ChemComp-FBP / 1,6-di-O-phosphono-beta-D-fructofuranose / BETA-FRUCTOSE-1,6-DIPHOSPHATE / FRUCTOSE-1,6-BISPHOSPHATE / 1,6-di-O-phosphono-beta-D-fructose / 1,6-di-O-phosphono-D-fructose / 1,6-di-O-phosphono-fructose


Type: D-saccharide, beta linking / Mass: 340.116 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C6H14O12P2
IdentifierTypeProgram
b-D-Fruf1PO36PO3IUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0

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Non-polymers , 5 types, 1564 molecules

#2: Chemical
ChemComp-I0R / 6-[(4-hydroxyphenyl)methyl]-2,4-dimethyl-4,6-dihydro-5H-[1,3]thiazolo[5',4':4,5]pyrrolo[2,3-d]pyridazin-5-one


Mass: 326.373 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C16H14N4O2S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-PYR / PYRUVIC ACID


Mass: 88.062 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H4O3
#5: Chemical
ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Mn
#6: Chemical ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: K
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1544 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY

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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: 2.73 Å3/Da / Density % sol: 55 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 10 mM MnSO4, 50 mM MES/KOH pH 6.5, 10 %(w/v) PEG 8000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97918 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 7, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.35→49.88 Å / Num. obs: 213360 / % possible obs: 99.57 % / Redundancy: 5.7 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 23.8
Reflection shellResolution: 2.35→2.434 Å / Rmerge(I) obs: 0.535 / Mean I/σ(I) obs: 3.9 / Num. unique obs: 20443

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Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.35→49.88 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.96 / Phase error: 26.8 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2457 10677 5.01 %
Rwork0.2016 --
obs0.2038 213233 99.59 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.35→49.88 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms28996 0 298 1544 30838
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00429774
X-RAY DIFFRACTIONf_angle_d0.67540382
X-RAY DIFFRACTIONf_dihedral_angle_d22.124272
X-RAY DIFFRACTIONf_chiral_restr0.0464668
X-RAY DIFFRACTIONf_plane_restr0.0045256
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.35-2.380.31423050.26376001X-RAY DIFFRACTION90
2.38-2.40.32263790.26366760X-RAY DIFFRACTION100
2.4-2.430.29483710.24756627X-RAY DIFFRACTION100
2.43-2.460.29093570.24416763X-RAY DIFFRACTION100
2.46-2.50.27513550.23416677X-RAY DIFFRACTION100
2.5-2.530.28323400.22786691X-RAY DIFFRACTION100
2.53-2.570.27393730.22666765X-RAY DIFFRACTION100
2.57-2.610.26963550.2256673X-RAY DIFFRACTION100
2.61-2.650.2683630.22876699X-RAY DIFFRACTION100
2.65-2.690.2913540.22976777X-RAY DIFFRACTION100
2.69-2.740.29033310.22436715X-RAY DIFFRACTION100
2.74-2.790.26173470.21996731X-RAY DIFFRACTION100
2.79-2.840.2943510.22086782X-RAY DIFFRACTION100
2.84-2.90.27243350.2226751X-RAY DIFFRACTION100
2.9-2.960.27783820.21856684X-RAY DIFFRACTION100
2.96-3.030.25173680.21016730X-RAY DIFFRACTION100
3.03-3.110.25283470.2076766X-RAY DIFFRACTION100
3.11-3.190.26923550.21646715X-RAY DIFFRACTION100
3.19-3.280.26163490.21196806X-RAY DIFFRACTION100
3.28-3.390.25623670.2136747X-RAY DIFFRACTION100
3.39-3.510.2573620.20556804X-RAY DIFFRACTION100
3.51-3.650.25013360.19336770X-RAY DIFFRACTION100
3.65-3.820.2093540.18266813X-RAY DIFFRACTION100
3.82-4.020.20443540.17866811X-RAY DIFFRACTION100
4.02-4.270.20653330.16996840X-RAY DIFFRACTION100
4.27-4.60.20493760.15746839X-RAY DIFFRACTION100
4.6-5.060.20993630.17096844X-RAY DIFFRACTION100
5.06-5.790.24823340.19786936X-RAY DIFFRACTION100
5.79-7.290.23953900.21216939X-RAY DIFFRACTION100
7.3-49.880.24433910.2087100X-RAY DIFFRACTION98
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)
11.6633-0.21310.68780.5226-0.27741.3018-0.006-0.31890.12620.0016-0.0362-0.1255-0.1250.01670.04380.271-0.04610.03650.4549-0.05580.41178.5912-15.7584-92.4717
21.083-0.81030.18531.952-0.13410.83530.52111.0217-0.5657-0.8271-0.4219-0.35060.51160.4776-0.05590.97060.17760.02951.0369-0.07750.98129.1026-42.1684-119.737
31.2144-0.02220.25910.6018-0.25711.21790.0508-0.1902-0.1192-0.0238-0.0462-0.02080.1152-0.02820.01930.2119-0.01940.00760.3273-0.00360.32560.3378-24.9091-96.8068
41.4922-0.3778-0.67731.00990.09371.0791-0.0551-0.13630.05230.09080.1318-0.0454-0.11290.2414-0.0550.23620.0011-0.01570.5055-0.00240.292-3.2256-13.77-73.4705
50.702-0.49480.7220.5169-0.44231.57060.04120.16980.0316-0.0844-0.0154-0.0924-0.07640.2749-0.03970.2878-0.04570.05460.3802-0.04230.3224-8.0126-11.6716-125.6037
61.98680.0886-0.34822.04420.06640.4602-0.00580.4594-0.2060.4174-0.2958-0.2118-0.05340.24440.07490.7423-0.276-0.01870.90090.13591.229417.23089.0556-113.9514
71.73230.12760.99720.4077-0.11071.1465-0.17980.25540.56780.09110.0513-0.1596-0.55950.69840.0340.6161-0.2205-0.03290.55030.00510.572-0.18229.4376-124.2551
81.6259-0.03190.630.1351-0.24760.8524-0.0545-0.01730.0808-0.03020.0496-0.0064-0.0406-0.0279-0.00190.2728-0.03020.0220.248-0.0340.2675-18.4261-8.1319-120.3892
90.50540.50210.90230.580.37071.7063-0.0037-0.112-0.03030.138-0.03750.01510.1199-0.06130.0910.22870.01540.03440.31960.0180.2835-45.1117-13.6-65.7172
101.9025-0.59361.44811.044-0.13861.7766-0.01460.15720.0578-0.1621-0.14410.5731-0.418-0.23760.15410.46920.156-0.04070.5445-0.00940.5018-54.17245.0494-67.7475
110.94540.22790.51591.8874-1.2782.1347-0.309-0.3140.43240.11580.18670.2213-0.642-0.34320.11610.47940.084-0.10130.425-0.08490.5793-46.257211.7688-61.5665
121.1260.07910.5630.80520.21140.9603-0.08840.03170.1426-0.0164-0.0261-0.0119-0.16250.07670.08430.2585-0.0243-0.01210.2690.03230.2903-45.2177-4.1804-74.9151
131.37630.0441-0.19540.6720.50371.0388-0.0472-0.0388-0.08490.08010.1095-0.10180.10850.1661-0.06890.25710.0253-0.01820.3163-0.00650.2665-25.5412-12.0432-62.108
140.9468-0.17130.9450.3280.33921.5747-0.1020.31260.2274-0.0204-0.02780.1188-0.18470.1080.0970.26370.02980.01810.41650.04040.3882-62.3851-10.5885-96.7928
151.10190.0938-0.1140.8001-0.03241.68190.1013-0.2962-0.39820.5343-0.00170.33940.2414-0.2643-0.05370.4742-0.09870.10680.42380.03930.5979-66.8297-36.1841-75.8076
160.9840.21060.34370.91240.0341.01980.03830.1049-0.17290.0267-0.06520.05430.17340.0240.03940.21230.02060.02240.2882-0.01110.3181-58.5737-25.8705-90.8774
17-0.00210.22090.08640.8570.240.8906-0.0882-0.02930.0378-0.19190.0517-0.1213-0.15140.39590.00030.2478-0.02770.01960.4010.05430.328-46.8574-11.2549-98.1975
181.62650.1091-0.7761.0730.22160.7754-0.07840.08260.1037-0.10230.1218-0.0133-0.0615-0.0579-0.0340.2616-0.02120.00550.347-0.01650.2719-52.0539-12.5403-115.7385
190.5730.2219-0.35792.19380.28980.7726-0.0991-0.3502-0.16260.2768-0.102-0.34860.74340.39740.11680.68930.0880.00240.38030.07260.394720.0237-76.8137-194.4221
200.80650.0413-0.30861.0255-0.64642.151-0.05440.1658-0.1154-0.1583-0.05030.18611.3423-0.8770.0881.0671-0.50960.04820.5495-0.09510.4103-2.1804-91.6984-203.4715
210.73990.321-0.12561.406-0.00841.4917-0.01030.0042-0.0769-0.2825-0.1153-0.06710.8461-0.10860.07310.9659-0.18810.04060.35560.01490.37857.3593-92.8784-180.7359
220.65390.51210.26840.9221-0.86492.34470.13720.13160.1531-0.07590.03560.12410.2568-0.6119-0.1360.2931-0.0067-0.04410.3298-0.01360.2917.2624-66.2347-224.0244
230.9136-0.897-0.1651.8909-0.57410.43230.14020.2125-0.5186-0.3447-0.17970.4050.3610.1991-0.0250.65180.27780.01650.5374-0.04510.581932.8444-87.4631-223.2664
240.36850.1322-0.35020.89720.13221.60670.01720.0650.0516-0.048-0.0502-0.02610.08390.0010.01510.26350.0495-0.01520.25010.03080.271315.0066-60.0602-216.8987
250.8631-0.27270.7612.1213-0.5741.4997-0.2442-0.04560.39620.0977-0.01110.0132-1.0142-0.31880.08760.87690.1762-0.09380.3154-0.06230.40075.7261-28.5817-177.9499
261.28920.0783-0.15821.7273-1.16111.98660.0063-0.20560.0471-0.19830.15150.6963-0.8983-1.3313-0.02080.79940.5765-0.06570.9659-0.06280.6071-15.9126-31.0948-178.0069
270.9497-0.07240.20580.6304-0.61641.4894-0.0481-0.07350.02920.1105-0.05420.056-0.6447-0.34240.10660.50310.1123-0.03470.3519-0.03090.3382.8813-39.5911-174.7398
280.5043-0.67180.26721.33650.33721.478-0.06580.02290.21890.2059-0.0987-0.0898-0.835-0.12470.15870.73680.1288-0.03280.30880.03790.39366.336-30.0883-197.8559
290.5809-0.32260.13040.7089-0.83742.02650.0817-0.2565-0.10410.04540.01310.052-0.0469-0.4659-0.07050.2332-0.02880.01580.298-0.02630.2566.8009-56.7527-154.6039
300.99471.0560.03682.0856-0.35930.68860.1334-0.28050.33110.2255-0.20580.3063-0.28970.14680.03270.454-0.2051-0.03720.4533-0.01950.450632.3913-35.6526-155.9698
310.7154-0.02190.30490.7632-0.26281.8559-0.0216-0.01610.02290.1194-0.0544-0.1214-0.22120.13680.06560.2892-0.0695-0.02660.2494-0.00250.289618.5339-52.3264-159.8369
320.80070.05370.5541.64980.11272.15260.1069-0.1395-0.1457-0.0251-0.08410.12030.5148-0.2166-0.00780.3806-0.0995-0.01920.30740.03850.3278.8318-75.644-163.7739
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 58 through 174 )
2X-RAY DIFFRACTION2chain 'A' and (resid 175 through 251 )
3X-RAY DIFFRACTION3chain 'A' and (resid 252 through 450 )
4X-RAY DIFFRACTION4chain 'A' and (resid 451 through 574 )
5X-RAY DIFFRACTION5chain 'B' and (resid 57 through 183 )
6X-RAY DIFFRACTION6chain 'B' and (resid 184 through 244 )
7X-RAY DIFFRACTION7chain 'B' and (resid 245 through 290 )
8X-RAY DIFFRACTION8chain 'B' and (resid 291 through 574 )
9X-RAY DIFFRACTION9chain 'C' and (resid 50 through 141 )
10X-RAY DIFFRACTION10chain 'C' and (resid 142 through 265 )
11X-RAY DIFFRACTION11chain 'C' and (resid 266 through 301 )
12X-RAY DIFFRACTION12chain 'C' and (resid 302 through 450 )
13X-RAY DIFFRACTION13chain 'C' and (resid 451 through 574 )
14X-RAY DIFFRACTION14chain 'D' and (resid 57 through 141 )
15X-RAY DIFFRACTION15chain 'D' and (resid 142 through 251 )
16X-RAY DIFFRACTION16chain 'D' and (resid 252 through 413 )
17X-RAY DIFFRACTION17chain 'D' and (resid 414 through 450 )
18X-RAY DIFFRACTION18chain 'D' and (resid 451 through 574 )
19X-RAY DIFFRACTION19chain 'E' and (resid 51 through 88 )
20X-RAY DIFFRACTION20chain 'E' and (resid 89 through 450 )
21X-RAY DIFFRACTION21chain 'E' and (resid 451 through 574 )
22X-RAY DIFFRACTION22chain 'F' and (resid 57 through 141 )
23X-RAY DIFFRACTION23chain 'F' and (resid 142 through 251 )
24X-RAY DIFFRACTION24chain 'F' and (resid 252 through 574 )
25X-RAY DIFFRACTION25chain 'G' and (resid 50 through 265 )
26X-RAY DIFFRACTION26chain 'G' and (resid 266 through 331 )
27X-RAY DIFFRACTION27chain 'G' and (resid 332 through 450 )
28X-RAY DIFFRACTION28chain 'G' and (resid 451 through 574 )
29X-RAY DIFFRACTION29chain 'H' and (resid 57 through 141 )
30X-RAY DIFFRACTION30chain 'H' and (resid 142 through 265 )
31X-RAY DIFFRACTION31chain 'H' and (resid 266 through 430 )
32X-RAY DIFFRACTION32chain 'H' and (resid 431 through 574 )

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  • 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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