[English] 日本語
Yorodumi
- PDB-6vfz: Crystal Structure of Human Mitochondrial Isocitrate Dehydrogenase... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vfz
TitleCrystal Structure of Human Mitochondrial Isocitrate Dehydrogenase (IDH2) R140Q Mutant Homodimer in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor.
ComponentsIsocitrate dehydrogenase [NADP], mitochondrial
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE inhibitor / IDH / ICD-M / IDP / NADP(+)-SPECIFIC ICDH / OXALOSUCCINATE DECARBOXYLASE / 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 / Mitochondrial protein degradation / tricarboxylic acid cycle / Transcriptional activation of mitochondrial biogenesis ...Citric acid cycle (TCA cycle) / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / Mitochondrial protein degradation / 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 / Isopropylmalate Dehydrogenase / Isopropylmalate Dehydrogenase / Isocitrate/isopropylmalate dehydrogenase, conserved site / Isocitrate and isopropylmalate dehydrogenases signature. / Isopropylmalate dehydrogenase-like domain / Isocitrate/isopropylmalate dehydrogenase / Isocitrate/isopropylmalate dehydrogenase / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-9UO / Chem-NDP / Isocitrate dehydrogenase [NADP], mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.99 Å
AuthorsPadyana, A. / Jin, L.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma.
Authors: Konteatis, Z. / Artin, E. / Nicolay, B. / Straley, K. / Padyana, A.K. / Jin, L. / Chen, Y. / Narayaraswamy, R. / Tong, S. / Wang, F. / Zhou, D. / Cui, D. / Cai, Z. / Luo, Z. / Fang, C. / ...Authors: Konteatis, Z. / Artin, E. / Nicolay, B. / Straley, K. / Padyana, A.K. / Jin, L. / Chen, Y. / Narayaraswamy, R. / Tong, S. / Wang, F. / Zhou, D. / Cui, D. / Cai, Z. / Luo, Z. / Fang, C. / Tang, H. / Lv, X. / Nagaraja, R. / Yang, H. / Su, S.M. / Sui, Z. / Dang, L. / Yen, K. / Popovici-Muller, J. / Codega, P. / Campos, C. / Mellinghoff, I.K. / Biller, S.A.
History
DepositionJan 7, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 4, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
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.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

-
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)105,5989
Polymers103,5662
Non-polymers2,0327
Water11,097616
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8850 Å2
ΔGint-109 kcal/mol
Surface area33290 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.068, 119.797, 130.973
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

-
Protein , 1 types, 2 molecules AB

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


Mass: 51783.008 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDH2 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P48735, isocitrate dehydrogenase (NADP+)

-
Non-polymers , 5 types, 623 molecules

#2: Chemical ChemComp-9UO / 6-(6-chloropyridin-2-yl)-N2,N4-bis[(2R)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine


Mass: 414.737 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H13ClF6N6 / Feature type: SUBJECT OF INVESTIGATION
#3: 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
#4: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 616 / 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: 2.24 Å3/Da / Density % sol: 45.02 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 200 mM CaCl2, 0.1M Tris-HCL pH8.5, 20% (w/v) PEG 4000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97853 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 29, 2015
RadiationMonochromator: Pilatus 3 6M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97853 Å / Relative weight: 1
ReflectionResolution: 1.99→50 Å / Num. obs: 63731 / % possible obs: 100 % / Redundancy: 12.7 % / Biso Wilson estimate: 22.32 Å2 / Rmerge(I) obs: 0.095 / Net I/σ(I): 8.1
Reflection shellResolution: 1.99→2.03 Å / Redundancy: 9.9 % / Rmerge(I) obs: 0.905 / Num. unique obs: 3146 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5I96

5i96


Resolution: 1.99→42.06 Å / SU ML: 0.1541 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 19.7411
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflectionSelection details
Rfree0.2091 3046 4.92 %Random selection
Rwork0.1774 58855 --
obs0.179 61901 96.26 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 34.23 Å2
Refinement stepCycle: LAST / Resolution: 1.99→42.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6537 0 127 616 7280
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00436905
X-RAY DIFFRACTIONf_angle_d0.67999368
X-RAY DIFFRACTIONf_chiral_restr0.04681008
X-RAY DIFFRACTIONf_plane_restr0.00451224
X-RAY DIFFRACTIONf_dihedral_angle_d15.47491011
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.99-2.020.2176950.21491706X-RAY DIFFRACTION62.06
2.02-2.060.24811240.19632159X-RAY DIFFRACTION79.57
2.06-2.090.24581330.20072335X-RAY DIFFRACTION86.2
2.09-2.130.27341220.19982540X-RAY DIFFRACTION92.53
2.13-2.170.24871390.19962682X-RAY DIFFRACTION97.78
2.17-2.220.25241390.19782738X-RAY DIFFRACTION99.31
2.22-2.260.21781490.18682743X-RAY DIFFRACTION99.9
2.26-2.320.23961270.18842737X-RAY DIFFRACTION99.79
2.32-2.370.21441430.18462765X-RAY DIFFRACTION99.97
2.37-2.440.22471450.1882755X-RAY DIFFRACTION99.97
2.44-2.510.241500.18252740X-RAY DIFFRACTION100
2.51-2.590.24591450.18592761X-RAY DIFFRACTION100
2.59-2.680.19941330.17392797X-RAY DIFFRACTION100
2.68-2.790.20221620.17782748X-RAY DIFFRACTION100
2.79-2.920.23091270.17592785X-RAY DIFFRACTION100
2.92-3.070.22571360.17812789X-RAY DIFFRACTION100
3.07-3.260.19861490.17282771X-RAY DIFFRACTION99.97
3.26-3.520.19321430.16672810X-RAY DIFFRACTION99.97
3.52-3.870.17751390.15852810X-RAY DIFFRACTION100
3.87-4.430.1891570.15132817X-RAY DIFFRACTION100
4.43-5.580.18191360.16322863X-RAY DIFFRACTION99.97
5.58-42.060.20161530.19923004X-RAY DIFFRACTION99.84
Refinement TLS params.Method: refined / Origin x: -32.4603290885 Å / Origin y: 11.3263287318 Å / Origin z: -25.900576091 Å
111213212223313233
T0.0424014639052 Å20.00936571545214 Å20.0262691180808 Å2-0.0774942103877 Å2-0.0327527576899 Å2--0.100584335515 Å2
L1.03117440611 °20.553458071843 °20.28282556478 °2-1.84903143232 °20.817894237463 °2--1.7777303736 °2
S-0.107524627338 Å °0.0908666810842 Å °0.00689006707011 Å °-0.0519646994264 Å °-0.0453691582714 Å °0.0649773887216 Å °-0.0847265951187 Å °-0.0832283988199 Å °0.0620971976408 Å °
Refinement TLS groupSelection details: all

+
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