[English] 日本語
Yorodumi
- PDB-8vha: Crystal Structure of Human IDH1 R132Q in complex with NADPH and A... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vha
TitleCrystal Structure of Human IDH1 R132Q in complex with NADPH and Alpha-Ketoglutarate
ComponentsIsocitrate dehydrogenase [NADP] cytoplasmic
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 / NADP+ metabolic process / 2-oxoglutarate metabolic process ...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 / NADP+ metabolic process / 2-oxoglutarate metabolic process / glyoxylate cycle / response to steroid hormone / female gonad development / peroxisomal matrix / tricarboxylic acid cycle / glutathione metabolic process / Peroxisomal protein import / NAD binding / tertiary granule lumen / peroxisome / NADP binding / secretory granule lumen / response to oxidative stress / 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 / Isocitrate/isopropylmalate dehydrogenase, conserved site / Isocitrate and isopropylmalate dehydrogenases signature. / Isopropylmalate dehydrogenase-like domain / Isocitrate/isopropylmalate dehydrogenase / Isocitrate/isopropylmalate dehydrogenase
Similarity search - Domain/homology
2-OXOGLUTARIC ACID / Chem-EE1 / Chem-NDP / NITRATE ION / Isocitrate dehydrogenase [NADP] cytoplasmic
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.28 Å
AuthorsMealka, M. / Sohl, C.D. / Huxford, T.
Funding support United States, 2items
OrganizationGrant numberCountry
American Cancer SocietyRSG-19-075-01-TBE United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R35 GM137773 United States
CitationJournal: Nat Commun / Year: 2024
Title: Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms.
Authors: Mealka, M. / Sierra, N.A. / Avellaneda Matteo, D. / Albekioni, E. / Khoury, R. / Mai, T. / Conley, B.M. / Coleman, N.J. / Sabo, K.A. / Komives, E.A. / Bobkov, A.A. / Cooksy, A.L. / Silletti, ...Authors: Mealka, M. / Sierra, N.A. / Avellaneda Matteo, D. / Albekioni, E. / Khoury, R. / Mai, T. / Conley, B.M. / Coleman, N.J. / Sabo, K.A. / Komives, E.A. / Bobkov, A.A. / Cooksy, A.L. / Silletti, S. / Schiffer, J.M. / Huxford, T. / Sohl, C.D.
History
DepositionDec 31, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 24, 2024Provider: repository / Type: Initial release
Revision 1.1May 22, 2024Group: 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

-
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)197,85517
Polymers194,0004
Non-polymers3,85413
Water8,323462
1
A: Isocitrate dehydrogenase [NADP] cytoplasmic
B: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules


Theoretical massNumber of molelcules
Total (without water)98,9859
Polymers97,0002
Non-polymers1,9857
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8380 Å2
ΔGint-70 kcal/mol
Surface area33170 Å2
MethodPISA
2
C: Isocitrate dehydrogenase [NADP] cytoplasmic
D: Isocitrate dehydrogenase [NADP] cytoplasmic
hetero molecules


Theoretical massNumber of molelcules
Total (without water)98,8698
Polymers97,0002
Non-polymers1,8696
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8910 Å2
ΔGint-70 kcal/mol
Surface area32440 Å2
MethodPISA
Unit cell
Length a, b, c (Å)83.821, 104.860, 107.711
Angle α, β, γ (deg.)90.00, 98.19, 90.00
Int Tables number4
Space group name H-MP1211
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Isocitrate dehydrogenase [NADP] cytoplasmic / IDH / IDH1 / Cytosolic NADP-isocitrate dehydrogenase / IDPc / NADP(+)-specific ICDH / ...IDH / IDH1 / Cytosolic NADP-isocitrate dehydrogenase / IDPc / NADP(+)-specific ICDH / Oxalosuccinate decarboxylase


Mass: 48500.117 Da / Num. of mol.: 4 / Mutation: R132Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDH1, PICD / Production host: Escherichia coli (E. coli)
References: UniProt: O75874, isocitrate dehydrogenase (NADP+)

-
Non-polymers , 7 types, 475 molecules

#2: Chemical ChemComp-EE1 / (3~{S})-3-[(4~{S})-3-aminocarbonyl-1-[(2~{R},3~{R},4~{S},5~{R})-5-[[[[(2~{R},3~{R},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3-oxidanyl-4-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]-4~{H}-pyridin-4-yl]-2-oxidanylidene-pentanedioic acid / NADPH with ketoglutarate adduct


Mass: 889.503 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H34N7O22P3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-NO3 / NITRATE ION


Mass: 62.005 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: NO3
#4: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Ca
#5: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3 / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-AKG / 2-OXOGLUTARIC ACID


Mass: 146.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H6O5 / Feature type: SUBJECT OF INVESTIGATION
#7: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 462 / 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: 2.42 Å3/Da / Density meas: 49.2 Mg/m3 / Density % sol: 49.07 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 6.8 / Details: 160mM NaNO3 and 20% W/V PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.97946 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jan 22, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.28→39.15 Å / Num. obs: 82740 / % possible obs: 98.28 % / Redundancy: 2 % / Biso Wilson estimate: 35.61 Å2 / CC1/2: 0.997 / Net I/σ(I): 10.65
Reflection shellResolution: 2.28→2.36 Å / Num. unique obs: 2247 / CC1/2: 0.748

-
Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
XDSdata reduction
XDSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.28→39.15 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.06 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2223 4053 4.9 %
Rwork0.1673 --
obs0.1701 82740 98.16 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.28→39.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13053 0 228 462 13743
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00913584
X-RAY DIFFRACTIONf_angle_d0.92318360
X-RAY DIFFRACTIONf_dihedral_angle_d8.5391811
X-RAY DIFFRACTIONf_chiral_restr0.0541977
X-RAY DIFFRACTIONf_plane_restr0.0072338
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.28-2.310.2971160.22612447X-RAY DIFFRACTION89
2.31-2.330.28561380.2132720X-RAY DIFFRACTION98
2.33-2.360.29741230.21892698X-RAY DIFFRACTION99
2.36-2.390.28071470.21452775X-RAY DIFFRACTION99
2.39-2.430.27691330.20842708X-RAY DIFFRACTION99
2.43-2.460.28921340.20252743X-RAY DIFFRACTION99
2.46-2.50.29291470.20642700X-RAY DIFFRACTION99
2.5-2.540.28091550.20482716X-RAY DIFFRACTION99
2.54-2.580.29571410.19932703X-RAY DIFFRACTION99
2.58-2.620.27431300.2012730X-RAY DIFFRACTION98
2.62-2.670.24451300.19992692X-RAY DIFFRACTION98
2.67-2.720.27221320.20552721X-RAY DIFFRACTION98
2.72-2.780.29651580.19942654X-RAY DIFFRACTION97
2.78-2.840.30151220.19752663X-RAY DIFFRACTION96
2.84-2.90.26631560.19682727X-RAY DIFFRACTION99
2.9-2.980.2561590.19312716X-RAY DIFFRACTION99
2.98-3.060.25891480.18662724X-RAY DIFFRACTION99
3.06-3.150.2571370.19072738X-RAY DIFFRACTION99
3.15-3.250.24651160.192750X-RAY DIFFRACTION99
3.25-3.360.25241530.18142767X-RAY DIFFRACTION99
3.36-3.50.21531340.16922734X-RAY DIFFRACTION98
3.5-3.660.22641270.16042672X-RAY DIFFRACTION97
3.66-3.850.21211790.14822681X-RAY DIFFRACTION98
3.85-4.090.18581380.13972732X-RAY DIFFRACTION99
4.09-4.410.13721340.12272768X-RAY DIFFRACTION99
4.41-4.850.16021370.12642759X-RAY DIFFRACTION99
4.85-5.550.18651440.14242679X-RAY DIFFRACTION96
5.55-6.990.22461550.16322775X-RAY DIFFRACTION99
6.99-39.150.14451300.13612795X-RAY DIFFRACTION98
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)
11.6033-0.1831-0.82651.851-0.54442.3895-0.03990.1272-0.1672-0.40750.06570.35320.6768-0.4016-0.00770.4052-0.0829-0.0690.25570.01710.2981-15.9804-8.97799.5584
21.1069-0.2312-0.13561.35630.53531.8932-0.0240.01830.1731-0.07170.1225-0.0373-0.2238-0.1071-0.1050.2611-0.0147-0.01450.24550.03870.28188.295-4.0466-0.9299
31.6871-0.10090.27120.94870.96373.44080.0783-0.16140.03710.10120.04810.110.3675-0.3885-0.12560.2658-0.0490.00550.21890.02750.2578-15.2003-2.550121.2743
41.15040.11011.27242.6048-1.37464.7117-0.09550.30310.0387-0.32410.0384-0.3047-0.2840.36990.08030.3158-0.03790.07510.34610.01630.415338.321-7.91887.7621
50.64460.1290.24940.15420.00531.1988-0.0202-0.0515-0.0796-0.00220.0654-0.08320.1107-0.066-0.05260.28240.0130.00040.23820.01140.255815.1445-19.197510.1042
61.557-0.4001-0.11164.29670.00841.7791-0.0222-0.20150.15050.07690.0039-0.2766-0.35730.11840.03290.2411-0.0353-0.02890.2752-0.0390.352534.4293-2.255425.8979
71.8371-0.25230.47231.75540.12763.27390.27060.1176-0.2684-0.30610.0144-0.16250.56161.2427-0.29290.54460.1733-0.0851.2123-0.15730.572237.61141.533665.6917
80.72790.2513-0.2561.6668-0.2131.14370.0562-0.11040.11650.0735-0.0615-0.1201-0.13370.23960.01960.2369-0.0724-0.00460.37-0.01820.299213.11536.353475.6343
92.6304-1.21661.67740.7937-1.04621.68040.21750.77010.1646-0.3003-0.2757-0.1271-0.01542.1246-0.01550.4925-0.19960.0541.21040.02140.425332.253916.767458.1792
101.22310.12340.49931.0174-0.05533.18740.0217-0.0608-0.05270.13210.00030.06370.0398-0.4078-0.03650.2394-0.03920.020.30930.00370.2834-18.61991.244468.3443
110.8326-0.0180.05550.8184-0.37261.42780.01350.1052-0.0551-0.1581-0.0312-0.07390.16930.14030.02490.2572-0.01010.02190.2921-0.0290.27985.4663-4.311660.7415
121.23750.27660.26334.50931.29552.2773-0.00730.19610.1868-0.1891-0.08930.1306-0.2585-0.19080.11190.19330.01270.0010.28030.04780.2443-16.737215.264454.7642
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 0 through 133 )
2X-RAY DIFFRACTION2chain 'A' and (resid 134 through 285 )
3X-RAY DIFFRACTION3chain 'A' and (resid 286 through 413 )
4X-RAY DIFFRACTION4chain 'B' and (resid 3 through 94 )
5X-RAY DIFFRACTION5chain 'B' and (resid 95 through 312 )
6X-RAY DIFFRACTION6chain 'B' and (resid 313 through 413 )
7X-RAY DIFFRACTION7chain 'C' and (resid 4 through 94 )
8X-RAY DIFFRACTION8chain 'C' and (resid 95 through 285 )
9X-RAY DIFFRACTION9chain 'C' and (resid 286 through 411 )
10X-RAY DIFFRACTION10chain 'D' and (resid 4 through 94 )
11X-RAY DIFFRACTION11chain 'D' and (resid 95 through 312 )
12X-RAY DIFFRACTION12chain 'D' and (resid 313 through 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