[English] 日本語
Yorodumi
- PDB-6yb8: Human octameric PAICS in complex with CAIR and SAICAR -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6yb8
TitleHuman octameric PAICS in complex with CAIR and SAICAR
ComponentsMultifunctional protein ADE2Multi-function printer
KeywordsBIOSYNTHETIC PROTEIN / de novo purine biosynthesis / nucleotide metabolism / cancer target
Function / homology
Function and homology information


phosphoribosylaminoimidazole carboxylase / 5-amino-4-imidazole carboxylate lyase activity / phosphoribosylaminoimidazole carboxylase activity / phosphoribosylaminoimidazolesuccinocarboxamide synthase / phosphoribosylaminoimidazolesuccinocarboxamide synthase activity / 'de novo' XMP biosynthetic process / purine nucleobase biosynthetic process / Purine ribonucleoside monophosphate biosynthesis / 'de novo' AMP biosynthetic process / GMP biosynthetic process ...phosphoribosylaminoimidazole carboxylase / 5-amino-4-imidazole carboxylate lyase activity / phosphoribosylaminoimidazole carboxylase activity / phosphoribosylaminoimidazolesuccinocarboxamide synthase / phosphoribosylaminoimidazolesuccinocarboxamide synthase activity / 'de novo' XMP biosynthetic process / purine nucleobase biosynthetic process / Purine ribonucleoside monophosphate biosynthesis / 'de novo' AMP biosynthetic process / GMP biosynthetic process / 'de novo' IMP biosynthetic process / cadherin binding / extracellular exosome / ATP binding / membrane / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Class II PurE / SAICAR synthetase signature 1. / SAICAR synthetase signature 2. / SAICAR synthetase, conserved site / SAICAR synthetase/ADE2, N-terminal / SAICAR synthetase / PurE domain / AIR carboxylase / AIR carboxylase / Rossmann fold - #1970 ...Class II PurE / SAICAR synthetase signature 1. / SAICAR synthetase signature 2. / SAICAR synthetase, conserved site / SAICAR synthetase/ADE2, N-terminal / SAICAR synthetase / PurE domain / AIR carboxylase / AIR carboxylase / Rossmann fold - #1970 / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-C2R / IMIDAZOLE / Chem-OK8 / Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.36 Å
AuthorsSkerlova, J. / Unterlass, J. / Gottmann, M. / Homan, E. / Helleday, T. / Jemth, A.S. / Stenmark, P.
Funding support Sweden, European Union, Czech Republic, 3items
OrganizationGrant numberCountry
Swedish Research Council Sweden
European Research Council (ERC)695376European Union
Ministry of Education (MoE, Czech Republic)CZ.02.2.69/0.0/0.0/16_027/0008477 Czech Republic
CitationJournal: J.Biol.Chem. / Year: 2020
Title: Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.
Authors: Skerlova, J. / Unterlass, J. / Gottmann, M. / Marttila, P. / Homan, E. / Helleday, T. / Jemth, A.S. / Stenmark, P.
History
DepositionMar 16, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 24, 2024Group: 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
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Multifunctional protein ADE2
B: Multifunctional protein ADE2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)96,50118
Polymers94,2702
Non-polymers2,23116
Water8,143452
1
A: Multifunctional protein ADE2
B: Multifunctional protein ADE2
hetero molecules

A: Multifunctional protein ADE2
B: Multifunctional protein ADE2
hetero molecules

A: Multifunctional protein ADE2
B: Multifunctional protein ADE2
hetero molecules

A: Multifunctional protein ADE2
B: Multifunctional protein ADE2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)386,00472
Polymers377,0818
Non-polymers8,92364
Water1448
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_565-x,-y+1,z1
crystal symmetry operation3_555-x,y,-z1
crystal symmetry operation4_565x,-y+1,-z1
Buried area60110 Å2
ΔGint-80 kcal/mol
Surface area115930 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.878, 153.922, 223.565
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number23
Space group name H-MI222
Components on special symmetry positions
IDModelComponents
11A-671-

HOH

21A-795-

HOH

31B-927-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21C

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1010A7 - 425
2010C7 - 425

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Multifunctional protein ADE2 / Multi-function printer


Mass: 47135.102 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PAICS, ADE2, AIRC, PAIS / Production host: Escherichia coli (E. coli)
References: UniProt: P22234, phosphoribosylaminoimidazolesuccinocarboxamide synthase, phosphoribosylaminoimidazole carboxylase

-
Non-polymers , 5 types, 468 molecules

#2: Chemical ChemComp-C2R / 5-AMINO-1-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-1H-IMIDAZOLE-4-CARBOXYLIC ACID / CAIR / 4-CARBOXY-5-AMINOIMIDAZOLE RIBONUCLEOTIDE / 5′-Phosphoribosyl-4-carboxy-5-aminoimidazole


Mass: 339.196 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C9H14N3O9P / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-OK8 / (2~{S})-2-[[5-azanyl-1-[(2~{R},3~{R},4~{S},5~{R})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]imidazol-4-yl]car bonylamino]butanedioic acid / SAICAR / Phosphoribosylaminoimidazolesuccinocarboxamide


Mass: 454.283 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H19N4O12P / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-IMD / IMIDAZOLE / Imidazole


Mass: 69.085 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H5N2
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 452 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.78 Å3/Da / Density % sol: 55.72 % / Description: needles
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop
Details: 16 mg/ml PAICS with 5 mM SAICAR; 0.1 M MES/imidazole pH 6.5, 10% w/v PEG 8000, 20% v/v ethylene glycol, 0.02 M sodium L-glutamate, 0.02 M DL-alanine, 0.02 M glycine, 0.02 M DL-lysine HCl, and 0.02 M DL-serine

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 29, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.36→47.15 Å / Num. obs: 43523 / % possible obs: 99.8 % / Redundancy: 13.827 % / Biso Wilson estimate: 37.375 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.256 / Rrim(I) all: 0.266 / Χ2: 1.058 / Net I/σ(I): 8.39 / Num. measured all: 601806
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.36-2.5114.3121.1521.8198134691468570.7751.19599.2
2.51-2.6814.3110.8472.6193866655965590.8770.878100
2.68-2.8914.1420.6093.8786208610060960.9330.63299.9
2.89-3.1713.7950.4345.6477528562656200.9620.45199.9
3.17-3.5412.9930.2738.966173509850930.9840.28599.9
3.54-4.0812.1440.16813.7655536457345730.9920.175100
4.08-4.9914.6420.12919.2856487385838580.9960.134100
4.99-7.0214.3510.15116.2543857305630560.9950.156100
7.02-47.1513.2620.08226.4724017182118110.9980.08599.5

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
XSCALEdata scaling
MOLREPphasing
REFMAC5.8.0232refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2h31

2h31


Resolution: 2.36→47.15 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.932 / SU R Cruickshank DPI: 0.3176 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.318 / ESU R Free: 0.235
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2354 2177 5 %RANDOM
Rwork0.1773 ---
obs0.1802 41346 99.78 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 145.9 Å2 / Biso mean: 39.085 Å2 / Biso min: 17.02 Å2
Baniso -1Baniso -2Baniso -3
1--0.71 Å20 Å20 Å2
2--2.44 Å20 Å2
3----1.73 Å2
Refinement stepCycle: final / Resolution: 2.36→47.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6528 0 146 452 7126
Biso mean--53.27 38.38 -
Num. residues----838
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0136802
X-RAY DIFFRACTIONr_bond_other_d0.0350.0176396
X-RAY DIFFRACTIONr_angle_refined_deg1.641.6469193
X-RAY DIFFRACTIONr_angle_other_deg2.341.57914914
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.4755836
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.31323.419310
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.894151208
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.8391532
X-RAY DIFFRACTIONr_chiral_restr0.070.2889
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.027447
X-RAY DIFFRACTIONr_gen_planes_other0.0120.021327
Refine LS restraints NCS

Ens-ID: 1 / Number: 12937 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.11 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 2.363→2.424 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.366 156 -
Rwork0.329 2941 -
all-3097 -
obs--97.98 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

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

-
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

Read more