[English] 日本語
Yorodumi
- PDB-7pjn: Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7pjn
TitleCrystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor DS-1001B
Components(Isocitrate dehydrogenase [NADP] ...) x 2
KeywordsOXIDOREDUCTASE
Function / homology
Function and homology information


Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate / NADPH regeneration / regulation of phospholipid catabolic process / regulation of phospholipid biosynthetic process / NFE2L2 regulating TCA cycle genes / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / female gonad development / NADPH regeneration ...Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate / NADPH regeneration / regulation of phospholipid catabolic process / regulation of phospholipid biosynthetic process / NFE2L2 regulating TCA cycle genes / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / female gonad development / NADPH regeneration / NADP+ metabolic process / 2-oxoglutarate metabolic process / glyoxylate cycle / response to steroid hormone / peroxisomal matrix / tricarboxylic acid cycle / glutathione metabolic process / Peroxisomal protein import / NAD binding / peroxisome / tertiary granule lumen / NADP binding / response to oxidative stress / secretory granule lumen / ficolin-1-rich granule lumen / cadherin binding / Neutrophil degranulation / magnesium ion binding / protein homodimerization activity / mitochondrion / extracellular exosome / extracellular region / identical protein binding / cytosol / cytoplasm
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-7SU / CITRIC ACID / Chem-NDP / Isocitrate dehydrogenase [NADP] cytoplasmic
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.45 Å
AuthorsReinbold, R. / Rabe, P. / Abboud, M.I. / Schofield, C.J. / Clifton, I.J.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Wellcome Trust106244/Z/14/Z United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/R506655/1 United Kingdom
CitationJournal: Nat Commun / Year: 2022
Title: Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors.
Authors: Reinbold, R. / Hvinden, I.C. / Rabe, P. / Herold, R.A. / Finch, A. / Wood, J. / Morgan, M. / Staudt, M. / Clifton, I.J. / Armstrong, F.A. / McCullagh, J.S.O. / Redmond, J. / Bardella, C. / ...Authors: Reinbold, R. / Hvinden, I.C. / Rabe, P. / Herold, R.A. / Finch, A. / Wood, J. / Morgan, M. / Staudt, M. / Clifton, I.J. / Armstrong, F.A. / McCullagh, J.S.O. / Redmond, J. / Bardella, C. / Abboud, M.I. / Schofield, C.J.
History
DepositionAug 24, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 13, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 19, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 9, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isocitrate dehydrogenase [NADP] cytoplasmic
B: Isocitrate dehydrogenase [NADP] cytoplasmic
C: Isocitrate dehydrogenase [NADP] cytoplasmic
D: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules


Theoretical massNumber of molelcules
Total (without water)197,86023
Polymers191,2224
Non-polymers6,63819
Water1,946108
1
A: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules

D: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules


Theoretical massNumber of molelcules
Total (without water)98,91811
Polymers95,5952
Non-polymers3,3239
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_554x,y,z-11
Buried area8820 Å2
ΔGint-52 kcal/mol
Surface area32680 Å2
MethodPISA
2
B: Isocitrate dehydrogenase [NADP] cytoplasmic
C: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules


Theoretical massNumber of molelcules
Total (without water)98,94212
Polymers95,6272
Non-polymers3,31510
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8930 Å2
ΔGint-51 kcal/mol
Surface area32680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)80.180, 153.050, 164.010
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Isocitrate dehydrogenase [NADP] ... , 2 types, 4 molecules ACDB

#1: Protein Isocitrate dehydrogenase [NADP] cytoplasmic / IDH / Cytosolic NADP-isocitrate dehydrogenase / IDP / NADP(+)-specific ICDH / Oxalosuccinate decarboxylase


Mass: 47797.406 Da / Num. of mol.: 3 / Mutation: R132C, S280F
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDH1, PICD / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: O75874, isocitrate dehydrogenase (NADP+)
#2: Protein Isocitrate dehydrogenase [NADP] cytoplasmic / IDH / Cytosolic NADP-isocitrate dehydrogenase / IDP / NADP(+)-specific ICDH / Oxalosuccinate decarboxylase


Mass: 47829.406 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDH1, PICD / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: O75874, isocitrate dehydrogenase (NADP+)

-
Non-polymers , 5 types, 127 molecules

#3: Chemical
ChemComp-7SU / (E)-3-(1-(5-(2-fluoropropan-2-yl)-3-(2,4,6-trichlorophenyl)isoxazole-4-carbonyl)-3-methyl-1H-indol-4-yl)acrylic acid / (2E)-3-(1-{[5-(2-Fluoropropan-2-yl)-3-(2,4,6-trichlorophenyl)-1,2-oxazol-4-yl]carbonyl}-3-methyl-1H-indol-4-yl)prop-2-enoic acid


Mass: 535.779 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C25H18Cl3FN2O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-CIT / CITRIC ACID


Mass: 192.124 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C6H8O7
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical
ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H30N7O17P3 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 108 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.63 Å3/Da / Density % sol: 53.26 % / Description: rectangle, 100x100
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7 / Details: 2 M Ammonium citrate tribasic, DTT 2 mM

-
Data collection

DiffractionMean temperature: 100 K / Ambient temp details: cryo / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9999 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 27, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 2.45→55.95 Å / Num. obs: 74987 / % possible obs: 100 % / Redundancy: 13.7 % / CC1/2: 1 / Rmerge(I) obs: 0.092 / Rpim(I) all: 0.026 / Rrim(I) all: 0.096 / Net I/σ(I): 18.9 / Num. measured all: 1025494
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.45-2.5113.32.217256854700.5130.6192.2971.299.7
10.96-55.95120.0211147695710.0060.02272.999.2

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
Aimless0.7.4data scaling
PDB_EXTRACT3.27data extraction
xia2data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5TQH

5tqh


Resolution: 2.45→55.36 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 26.39 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2284 3675 4.91 %
Rwork0.1856 71202 -
obs0.1877 74877 99.93 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 182.14 Å2 / Biso mean: 81.1665 Å2 / Biso min: 41.84 Å2
Refinement stepCycle: final / Resolution: 2.45→55.36 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms12372 0 668 109 13149
Biso mean--83.24 64.13 -
Num. residues----1623
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 26

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.45-2.480.35541330.3092692282599
2.48-2.520.30591510.294227022853100
2.52-2.550.37241170.281727252842100
2.55-2.590.35911550.274626902845100
2.59-2.630.36951080.281927102818100
2.63-2.670.29861170.275427702887100
2.67-2.720.34331270.262826862813100
2.72-2.770.30951410.251127462887100
2.77-2.820.28751580.249826452803100
2.82-2.880.31531380.24427652903100
2.88-2.940.30481440.23726942838100
2.94-3.010.28421610.237726792840100
3.01-3.090.291150.235327842899100
3.09-3.170.28781250.223627082833100
3.17-3.260.26271360.231427392875100
3.26-3.370.25131690.201326842853100
3.37-3.490.24931360.192127552891100
3.49-3.630.23111320.182527382870100
3.63-3.790.22221630.166427072870100
3.79-3.990.20081570.165527452902100
3.99-4.240.19281480.150227612909100
4.24-4.570.19711340.133527592893100
4.57-5.030.16141410.135227762917100
5.03-5.760.19361810.166127632944100
5.76-7.250.24011370.188828392976100
7.25-55.360.19181510.171729403091100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.8421-0.80531.08191.7787-0.41761.75480.0119-0.1250.0617-0.20320.0280.00010.0884-0.0309-0.06060.517-0.01870.00390.48440.0070.470839.128-10.839-17.4802
26.82372.451-2.36621.6046-1.67745.3741-0.32150.29820.4631-0.43330.0922-0.23940.1730.02370.25330.63630.11710.04670.49370.09540.676841.7473-39.0209-40.1465
31.87532.2916-0.19128.10750.48491.4432-0.03280.21190.1327-0.36530.14860.805-0.2690.044-0.12570.48640.0175-0.06420.4460.08610.464723.4387-18.4697-36.1971
42.74790.2358-0.37451.993-0.72382.0519-0.0990.12360.41-0.09470.0910.1361-0.1985-0.153-0.00440.53420.0117-0.06770.4682-0.00990.474735.351.5857-21.2926
51.5368-0.49640.80672.0677-0.93812.2964-0.031-0.0406-0.01860.0386-0.0079-0.03-0.0493-0.010.03210.4326-0.0369-0.01060.48050.01510.450947.9674-18.62358.5585
60.88030.02411.53848.12443.32816.99470.0964-0.08740.35390.1729-0.380.34840.074-0.50220.32390.3606-0.0206-0.01190.67250.03420.774419.3225-21.012632.828
73.52152.757-1.03144.8201-0.6311.6730.1572-0.1354-0.27810.0999-0.19470.05950.16190.00930.01680.4390.0195-0.04120.45530.02630.46643.5382-33.320824.7272
81.7742-0.04391.05462.5136-0.48713.2408-0.06380.18170.0040.0652-0.1212-0.5074-0.13430.61970.14110.42260.01690.01130.66750.10.570263.6028-20.434211.6663
92.70560.16730.08021.6134-0.41583.19910.1175-0.3934-0.37940.2546-0.11820.57480.1408-0.54380.01010.6539-0.08340.09050.6613-0.05780.742942.9043-21.780860.041
102.83662.38071.20175.43912.74512.22240.0904-0.11620.29770.22590.12780.2149-0.147-0.1676-0.24460.4279-0.02380.04490.5570.03630.566724.2123-16.800635.6102
117.5927-0.9571-0.65380.32770.07814.7781-0.0789-0.06660.7530.06650.09980.1256-0.42930.1639-0.02150.5383-0.02950.00560.4243-0.01360.705842.9687-6.595637.7241
123.7573-1.5234-0.88062.14410.8212.1786-0.0208-0.1672-0.45260.0919-0.02040.2520.32940.05410.03250.6417-0.06180.02620.5465-0.02030.571956.3302-20.96458.8952
132.079-0.3925-0.67162.93540.53463.0842-0.31770.2254-0.7888-0.2162-0.01930.50550.4597-0.22330.31040.7005-0.05190.14050.5381-0.09660.754537.3678-16.362895.1989
145.4345-0.8363-1.85231.22992.23374.1071-0.44520.07620.0446-0.3547-0.01-0.26670.09010.33010.4340.54750.02770.03350.4410.12880.600541.3693-38.4267124.4496
151.16-0.52121.46193.8735-0.47372.6922-0.0960.08030.1451-0.1787-0.069-0.6386-0.17050.31170.14990.6337-0.02730.1430.65670.05940.690750.345-14.5671113.1768
167.0263-4.0336-4.16625.04962.8134.88830.29390.7079-0.0435-0.7002-0.31130.4013-0.7556-0.32970.01660.794-0.02050.02020.4950.03590.489735.113-0.825694.724
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 3 through 132 )A3 - 132
2X-RAY DIFFRACTION2chain 'A' and (resid 133 through 185 )A133 - 185
3X-RAY DIFFRACTION3chain 'A' and (resid 186 through 287 )A186 - 287
4X-RAY DIFFRACTION4chain 'A' and (resid 288 through 412 )A288 - 412
5X-RAY DIFFRACTION5chain 'B' and (resid 2 through 132 )B2 - 132
6X-RAY DIFFRACTION6chain 'B' and (resid 133 through 185 )B133 - 185
7X-RAY DIFFRACTION7chain 'B' and (resid 186 through 312 )B186 - 312
8X-RAY DIFFRACTION8chain 'B' and (resid 313 through 411 )B313 - 411
9X-RAY DIFFRACTION9chain 'C' and (resid 3 through 132 )C3 - 132
10X-RAY DIFFRACTION10chain 'C' and (resid 133 through 203 )C133 - 203
11X-RAY DIFFRACTION11chain 'C' and (resid 204 through 285 )C204 - 285
12X-RAY DIFFRACTION12chain 'C' and (resid 286 through 415 )C286 - 415
13X-RAY DIFFRACTION13chain 'D' and (resid 2 through 132 )D2 - 132
14X-RAY DIFFRACTION14chain 'D' and (resid 133 through 185 )D133 - 185
15X-RAY DIFFRACTION15chain 'D' and (resid 186 through 312 )D186 - 312
16X-RAY DIFFRACTION16chain 'D' and (resid 313 through 413 )D313 - 413

+
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