[English] 日本語
Yorodumi
- PDB-4ja8: Complex of Mitochondrial Isocitrate Dehydrogenase R140Q Mutant wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ja8
TitleComplex of Mitochondrial Isocitrate Dehydrogenase R140Q Mutant with AGI-6780 Inhibitor
ComponentsIsocitrate dehydrogenase [NADP], mitochondrial
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / protein-inhibitor complex / metabolic enzyme oncometabolite / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


Citric acid cycle (TCA cycle) / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / tricarboxylic acid cycle / Transcriptional activation of mitochondrial biogenesis / peroxisome ...Citric acid cycle (TCA cycle) / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / tricarboxylic acid cycle / Transcriptional activation of mitochondrial biogenesis / peroxisome / NAD binding / carbohydrate metabolic process / mitochondrial matrix / magnesium ion binding / mitochondrion / extracellular exosome / cytosol
Similarity search - Function
Isocitrate dehydrogenase NADP-dependent / Isocitrate/isopropylmalate dehydrogenase, conserved site / Isocitrate and isopropylmalate dehydrogenases signature. / Isopropylmalate Dehydrogenase / Isopropylmalate Dehydrogenase / Isopropylmalate dehydrogenase-like domain / Isocitrate/isopropylmalate dehydrogenase / Isocitrate/isopropylmalate dehydrogenase / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-1K9 / Chem-NDP / Isocitrate dehydrogenase [NADP], mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.55 Å
AuthorsWei, W. / Chen, L. / Wu, M. / Jiang, F. / Travins, J. / Qian, K. / DeLaBarre, B.
CitationJournal: Science / Year: 2013
Title: Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation.
Authors: Wang, F. / Travins, J. / DeLaBarre, B. / Penard-Lacronique, V. / Schalm, S. / Hansen, E. / Straley, K. / Kernytsky, A. / Liu, W. / Gliser, C. / Yang, H. / Gross, S. / Artin, E. / Saada, V. / ...Authors: Wang, F. / Travins, J. / DeLaBarre, B. / Penard-Lacronique, V. / Schalm, S. / Hansen, E. / Straley, K. / Kernytsky, A. / Liu, W. / Gliser, C. / Yang, H. / Gross, S. / Artin, E. / Saada, V. / Mylonas, E. / Quivoron, C. / Popovici-Muller, J. / Saunders, J.O. / Salituro, F.G. / Yan, S. / Murray, S. / Wei, W. / Gao, Y. / Dang, L. / Dorsch, M. / Agresta, S. / Schenkein, D.P. / Biller, S.A. / Su, S.M. / de Botton, S. / Yen, K.E.
History
DepositionFeb 18, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 10, 2013Provider: repository / Type: Initial release
Revision 1.1Apr 17, 2013Group: Database references
Revision 1.2May 15, 2013Group: Database references
Revision 1.3Nov 15, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.4Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn / 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 / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _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.ptnr1_label_seq_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 / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isocitrate dehydrogenase [NADP], mitochondrial
B: Isocitrate dehydrogenase [NADP], mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)96,68811
Polymers94,2672
Non-polymers2,4219
Water13,439746
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area9510 Å2
ΔGint-87 kcal/mol
Surface area33270 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.656, 119.661, 125.542
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Isocitrate dehydrogenase [NADP], mitochondrial / IDH / ICD-M / IDP / NADP(+)-specific ICDH / Oxalosuccinate decarboxylase


Mass: 47133.734 Da / Num. of mol.: 2 / Fragment: UNP Residues 41-452 / Mutation: R140Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDH2
References: UniProt: P48735, isocitrate dehydrogenase (NADP+)

-
Non-polymers , 5 types, 755 molecules

#2: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#3: Chemical ChemComp-1K9 / 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-yl-phenyl]-3-[3-(trifluoromethyl)phenyl]urea


Mass: 481.511 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H18F3N3O3S2
#4: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#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: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 746 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.34 Å3/Da / Density % sol: 47.36 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 8.5
Details: Crystals of the IDH2/R140Q:AGI-6780 complex were grown by hanging drop vapor diffusion at 18C after mixing the IDH2/R140Q:AGI-6780 sample with a 2 to 1 volume of protein to reservoir ...Details: Crystals of the IDH2/R140Q:AGI-6780 complex were grown by hanging drop vapor diffusion at 18C after mixing the IDH2/R140Q:AGI-6780 sample with a 2 to 1 volume of protein to reservoir solution. Reservoir solution was comprised of 0.2 M Calcium chloride, 0.1 M TRIS (pH 8.5) and 25 % w/v PEG 4000. Seeding methods were used to grow diffraction quality crystals, VAPOR DIFFUSION, temperature 298K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 1.5418 Å
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.55→50 Å / Num. obs: 128343 / % possible obs: 99.8 % / Redundancy: 6.7 % / Rmerge(I) obs: 0.054 / Χ2: 0.998 / Net I/σ(I): 13.9
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.55-1.614.90.422125220.986198.8
1.61-1.676.30.342126841.003199.8
1.67-1.756.60.265127200.9941100
1.75-1.846.70.184127370.9931100
1.84-1.956.70.1271279511100
1.95-2.16.80.0921279311100
2.1-2.3270.074128060.9951100
2.32-2.657.40.054129171.0131100
2.65-3.347.40.047129730.9991100
3.34-507.20.026133960.991199.8

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
REFMAC5.5.0109refinement
PDB_EXTRACT3.11data extraction
DENZOdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.55→31.9 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.943 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 1.438 / SU ML: 0.053 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.083 / ESU R Free: 0.086 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2179 6429 5 %RANDOM
Rwork0.1816 ---
obs0.1834 127987 99.51 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 75.96 Å2 / Biso mean: 21.3273 Å2 / Biso min: 4.32 Å2
Baniso -1Baniso -2Baniso -3
1--0.01 Å20 Å20 Å2
2--0 Å20 Å2
3---0.01 Å2
Refinement stepCycle: LAST / Resolution: 1.55→31.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6537 0 154 746 7437
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0280.0227061
X-RAY DIFFRACTIONr_angle_refined_deg2.1451.9729584
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2175856
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.08224.308318
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.552151228
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.281536
X-RAY DIFFRACTIONr_chiral_restr0.2850.21033
X-RAY DIFFRACTIONr_gen_planes_refined0.0130.0215324
X-RAY DIFFRACTIONr_mcbond_it1.31.54185
X-RAY DIFFRACTIONr_mcangle_it2.126786
X-RAY DIFFRACTIONr_scbond_it3.18732876
X-RAY DIFFRACTIONr_scangle_it4.7214.52792
LS refinement shellResolution: 1.55→1.59 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.307 479 -
Rwork0.269 8533 -
all-9012 -
obs--96.68 %

+
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