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- PDB-6dxw: Human N-acylethanolamine-hydrolyzing acid amidase (NAAA) precurso... -

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Basic information

Entry
Database: PDB / ID: 6dxw
TitleHuman N-acylethanolamine-hydrolyzing acid amidase (NAAA) precursor (C126A)
ComponentsN-acylethanolamine-hydrolyzing acid amidase
KeywordsHYDROLASE / endocannabinoid / lipase
Function / homology
Function and homology information


Neurotransmitter release cycle / N-(long-chain-acyl)ethanolamine deacylase / N-(long-chain-acyl)ethanolamine deacylase activity / N-acylethanolamine metabolic process / sphingosine metabolic process / ceramidase / N-acylsphingosine amidohydrolase activity / ceramidase activity / N-acylphosphatidylethanolamine metabolic process / fatty acid amide hydrolase activity ...Neurotransmitter release cycle / N-(long-chain-acyl)ethanolamine deacylase / N-(long-chain-acyl)ethanolamine deacylase activity / N-acylethanolamine metabolic process / sphingosine metabolic process / ceramidase / N-acylsphingosine amidohydrolase activity / ceramidase activity / N-acylphosphatidylethanolamine metabolic process / fatty acid amide hydrolase activity / hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds / extrinsic component of membrane / lipid catabolic process / lysosomal lumen / fatty acid metabolic process / DNA-binding transcription factor binding / lysosome / extracellular exosome / cytoplasm
Similarity search - Function
Acid ceramidase-like / Acid ceramidase, N-terminal / beta subunit of N-acylethanolamine-hydrolyzing acid amidase / Choloylglycine hydrolase/NAAA C-terminal / Linear amide C-N hydrolases, choloylglycine hydrolase family
Similarity search - Domain/homology
N-acylethanolamine-hydrolyzing acid amidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsGorelik, A. / Gebai, A. / Illes, K. / Piomelli, D. / Nagar, B.
Funding support Canada, 1items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)MOP-133535 Canada
CitationJournal: Proc. Natl. Acad. Sci. U.S.A. / Year: 2018
Title: Molecular mechanism of activation of the immunoregulatory amidase NAAA.
Authors: Gorelik, A. / Gebai, A. / Illes, K. / Piomelli, D. / Nagar, B.
History
DepositionJul 1, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 26, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 10, 2018Group: Data collection / Database references / Structure summary
Category: citation / entity
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year / _entity.formula_weight
Revision 1.2Oct 24, 2018Group: Data collection / Database references / Structure summary
Category: citation / citation_author / entity
Item: _citation.journal_abbrev / _citation.pdbx_database_id_PubMed ..._citation.journal_abbrev / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _entity.formula_weight
Revision 1.3Nov 7, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.4Apr 17, 2019Group: Data collection / Structure summary / Category: entity / struct / Item: _entity.pdbx_ec / _struct.pdbx_descriptor
Revision 1.5Jan 8, 2020Group: Author supporting evidence / Data collection / Category: chem_comp / pdbx_audit_support
Item: _chem_comp.type / _pdbx_audit_support.funding_organization
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...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 / 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 / _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.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
Revision 2.1Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: N-acylethanolamine-hydrolyzing acid amidase
B: N-acylethanolamine-hydrolyzing acid amidase
C: N-acylethanolamine-hydrolyzing acid amidase
D: N-acylethanolamine-hydrolyzing acid amidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)158,17341
Polymers154,2884
Non-polymers3,88537
Water15,421856
1
A: N-acylethanolamine-hydrolyzing acid amidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,3958
Polymers38,5721
Non-polymers8237
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: N-acylethanolamine-hydrolyzing acid amidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,80716
Polymers38,5721
Non-polymers1,23515
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: N-acylethanolamine-hydrolyzing acid amidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,03611
Polymers38,5721
Non-polymers1,46410
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: N-acylethanolamine-hydrolyzing acid amidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,9356
Polymers38,5721
Non-polymers3635
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)87.909, 140.011, 90.123
Angle α, β, γ (deg.)90.00, 115.20, 90.00
Int Tables number4
Space group name H-MP1211

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Components

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Protein , 1 types, 4 molecules ABCD

#1: Protein
N-acylethanolamine-hydrolyzing acid amidase / Acid ceramidase-like protein / N-acylsphingosine amidohydrolase-like / ASAH-like protein


Mass: 38571.945 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NAAA, ASAHL, PLT / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q02083, N-(long-chain-acyl)ethanolamine deacylase

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Sugars , 4 types, 9 molecules

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


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 1
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)-[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.: 1
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
#5: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 5
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 , 2 types, 884 molecules

#6: Chemical...
ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 28 / Source method: obtained synthetically / Formula: Cl
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 856 / 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: 3.25 Å3/Da / Density % sol: 62.18 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 1 M LiCl, 0.1 M MES pH 6 and 10 % PEG 6000

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.98 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Sep 17, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 87300 / % possible obs: 100 % / Redundancy: 3.8 % / Net I/σ(I): 18.5
Reflection shellResolution: 2.3→2.38 Å

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Processing

Software
NameVersionClassification
PHENIX(1.10.1_2155)refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5U7Z
Resolution: 2.3→38.257 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.7
RfactorNum. reflection% reflection
Rfree0.1933 1796 2.22 %
Rwork0.1673 --
obs0.1679 80800 92.4 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.3→38.257 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10424 0 216 856 11496
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00510918
X-RAY DIFFRACTIONf_angle_d0.85114926
X-RAY DIFFRACTIONf_dihedral_angle_d9.7726394
X-RAY DIFFRACTIONf_chiral_restr0.0531686
X-RAY DIFFRACTIONf_plane_restr0.0051901
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.36220.259870.21524002X-RAY DIFFRACTION61
2.3622-2.43170.26191100.2144630X-RAY DIFFRACTION71
2.4317-2.51020.27241170.21665346X-RAY DIFFRACTION81
2.5102-2.59990.22851380.20575900X-RAY DIFFRACTION90
2.5999-2.70390.24321450.20286427X-RAY DIFFRACTION98
2.7039-2.82690.22741490.18816592X-RAY DIFFRACTION100
2.8269-2.97590.21421510.18256549X-RAY DIFFRACTION100
2.9759-3.16230.19451540.17136541X-RAY DIFFRACTION100
3.1623-3.40630.17331470.16246602X-RAY DIFFRACTION100
3.4063-3.74890.18431450.15766567X-RAY DIFFRACTION100
3.7489-4.29070.18011490.14226576X-RAY DIFFRACTION100
4.2907-5.40340.13431510.12936593X-RAY DIFFRACTION100
5.4034-38.26210.20181530.17466679X-RAY DIFFRACTION100
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)
13.9534-0.1298-2.49792.23030.84774.7385-0.18640.13230.4646-0.3388-0.146-0.1901-0.3181-0.04280.25910.36490.075-0.04320.20820.10190.4185-25.248724.1362-17.8971
25.50049.6859-0.15022.0020.02051.2567-0.38710.4155-0.1847-1.03250.236-0.4619-0.10180.13070.18240.50540.03110.02870.4701-0.03660.4166-32.844513.8684-31.8144
34.55111.59472.18176.06262.16233.5718-0.2030.3230.4974-0.2813-0.1090.3696-0.3861-0.31010.25320.27710.0606-0.07010.3808-0.0240.2531-40.990613.4405-21.3145
42.347-0.96910.04532.5625-0.91521.1628-0.03620.22920.5131-0.1793-0.0862-0.1255-0.1521-0.06370.13410.18930.0159-0.00530.14270.03360.2676-19.21810.6523-15.0911
56.3202-0.93962.12921.2225-0.08982.20760.22130.4064-0.3298-0.178-0.12920.14010.1954-0.4709-0.00560.243-0.0119-0.00070.2734-0.02610.1574-34.0025-0.2892-17.1851
63.1254-0.11120.61062.1634-0.35272.15170.01880.14280.1241-0.1258-0.1157-0.25890.10560.06950.06930.16580.02190.0130.09460.01910.1373-17.7160.6845-12.6699
72.80170.98060.21730.339-0.06562.5798-0.0211-0.505-0.47360.1093-0.3045-0.47240.21960.11890.29990.3656-0.0203-0.08040.29170.16490.493516.4164-19.234723.9108
85.81240.0594-0.35113.5114-0.0732.52250.1496-0.1532-0.6871-0.0151-0.3297-0.6960.49990.23830.20480.3204-0.0083-0.0090.18160.07910.42858.4645-25.273812.7314
92.0431-0.3771-0.11892.5412-0.23252.25250.011-0.1173-0.14530.2168-0.1532-0.46640.05010.11970.16040.1804-0.0512-0.07020.20390.0890.234116.5241-4.752318.6444
101.43760.55760.16242.40770.22061.66840.056-0.1095-0.03820.1017-0.1641-0.1629-0.14150.03420.12390.149-0.03860.00150.1410.05660.191210.08460.534512.6144
111.4133-2.31132.05366.7527-2.56023.14780.11290.2082-0.2826-0.6509-0.1965-0.04210.02080.02050.12440.39170.0562-0.01430.1707-0.06750.2873-25.4491-38.1447-14.0794
126.61515.05549.10896.61175.87312.0043-0.14060.16340.2311-0.56250.0080.0305-0.2395-0.14330.1090.47760.0498-0.10090.25710.04630.393-15.5561-21.9707-11.5067
134.08571.5536-0.55814.90790.71722.4915-0.04780.1524-0.4848-0.2562-0.0264-0.53320.33540.1970.03680.21610.04130.0080.15650.00160.338-9.8505-31.8578-4.4081
140.8565-0.1462-0.43691.50420.09911.61090.17670.037-0.1663-0.0918-0.14470.23290.08670.0459-0.04870.19340.0048-0.05130.1174-0.04340.2966-32.6044-32.5453-2.0104
155.33441.8703-0.94392.27420.20820.36180.3218-0.44720.30390.1127-0.2085-0.0699-0.1160.1171-0.04580.2493-0.1026-0.00110.1729-0.02440.3232-18.215-27.15118.3802
162.5943-0.2478-0.11891.9293-0.25040.96890.2935-0.48060.22140.2233-0.16610.2155-0.0666-0.0224-0.09710.2395-0.09790.03370.1801-0.06440.3179-34.238-30.114710.6027
171.84430.1072-0.17137.8608-0.22812.68440.05390.19830.2061-0.50450.08060.566-0.0961-0.1579-0.04870.20990.0165-0.08060.1375-0.00290.3587-38.3558-26.4487-4.1313
180.90780.6009-0.13950.3775-0.09230.41230.039-0.4114-0.15120.2792-0.19050.06170.1448-0.40820.08740.6863-0.40870.23591.7163-0.30590.637-71.6647-12.338-21.2618
193.07820.3650.37241.50150.56421.03980.079-0.20170.0250.2888-0.31120.57810.1864-1.0550.19920.4731-0.21970.09981.3941-0.33820.2791-61.3978-1.472-20.8693
200.47950.0803-0.39931.24180.5082.2975-0.0011-0.61780.12320.2681-0.41270.26560.0812-0.49230.13650.4868-0.57690.25951.6203-0.1717-0.1119-69.7262-16.6872-35.7545
211.54770.87011.63141.79131.77222.9815-0.17140.05450.0630.01590.0673-0.12630.0121-0.1270.04710.3029-0.2373-0.14050.9453-0.20720.0025-54.1036-6.9316-34.0995
221.78530.65210.34741.39730.14562.13210.0051-0.56670.0005-0.0375-0.27880.07930.4675-0.79830.20270.4124-0.2243-0.0020.8289-0.08470.1868-61.2127-16.0137-45.4946
231.8876-1.39320.1581.7638-0.25951.5051-0.0176-0.2559-0.29440.4583-0.17540.13950.2403-0.21970.11860.6624-0.60640.19951.34680.0040.1633-68.7874-25.3719-35.3259
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 29 through 56 )
2X-RAY DIFFRACTION2chain 'A' and (resid 57 through 73 )
3X-RAY DIFFRACTION3chain 'A' and (resid 74 through 121 )
4X-RAY DIFFRACTION4chain 'A' and (resid 122 through 188 )
5X-RAY DIFFRACTION5chain 'A' and (resid 189 through 211 )
6X-RAY DIFFRACTION6chain 'A' and (resid 212 through 356 )
7X-RAY DIFFRACTION7chain 'B' and (resid 29 through 73 )
8X-RAY DIFFRACTION8chain 'B' and (resid 74 through 121 )
9X-RAY DIFFRACTION9chain 'B' and (resid 122 through 188 )
10X-RAY DIFFRACTION10chain 'B' and (resid 189 through 356 )
11X-RAY DIFFRACTION11chain 'C' and (resid 29 through 56 )
12X-RAY DIFFRACTION12chain 'C' and (resid 57 through 73 )
13X-RAY DIFFRACTION13chain 'C' and (resid 74 through 121 )
14X-RAY DIFFRACTION14chain 'C' and (resid 122 through 188 )
15X-RAY DIFFRACTION15chain 'C' and (resid 189 through 211 )
16X-RAY DIFFRACTION16chain 'C' and (resid 212 through 326 )
17X-RAY DIFFRACTION17chain 'C' and (resid 327 through 356 )
18X-RAY DIFFRACTION18chain 'D' and (resid 29 through 73 )
19X-RAY DIFFRACTION19chain 'D' and (resid 74 through 121 )
20X-RAY DIFFRACTION20chain 'D' and (resid 122 through 188 )
21X-RAY DIFFRACTION21chain 'D' and (resid 189 through 211 )
22X-RAY DIFFRACTION22chain 'D' and (resid 212 through 326 )
23X-RAY DIFFRACTION23chain 'D' and (resid 327 through 356 )

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Jul 12, 2017. Major update of PDB

Major update of PDB

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

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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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