[English] 日本語
Yorodumi
- PDB-9is9: human MTHFD2 in complex with LY374571 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9is9
Titlehuman MTHFD2 in complex with LY374571
ComponentsBifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
KeywordsOXIDOREDUCTASE / MTHFD2 / methylenetetrahydrofolate dehydrogenase 2 / 1C metabolism / mitochondria / OSIDOREDUCTASE
Function / homology
Function and homology information


methylenetetrahydrofolate dehydrogenase (NAD+) / methylenetetrahydrofolate dehydrogenase (NAD+) activity / formate biosynthetic process / methenyltetrahydrofolate cyclohydrolase / methenyltetrahydrofolate cyclohydrolase activity / methylenetetrahydrofolate dehydrogenase (NADP+) activity / Metabolism of folate and pterines / tetrahydrofolate metabolic process / tetrahydrofolate interconversion / phosphate ion binding ...methylenetetrahydrofolate dehydrogenase (NAD+) / methylenetetrahydrofolate dehydrogenase (NAD+) activity / formate biosynthetic process / methenyltetrahydrofolate cyclohydrolase / methenyltetrahydrofolate cyclohydrolase activity / methylenetetrahydrofolate dehydrogenase (NADP+) activity / Metabolism of folate and pterines / tetrahydrofolate metabolic process / tetrahydrofolate interconversion / phosphate ion binding / folic acid metabolic process / mitochondrial matrix / magnesium ion binding / mitochondrion / extracellular space
Similarity search - Function
Tetrahydrofolate dehydrogenase/cyclohydrolase signature 1. / Tetrahydrofolate dehydrogenase/cyclohydrolase signature 2. / Tetrahydrofolate dehydrogenase/cyclohydrolase, conserved site / Tetrahydrofolate dehydrogenase/cyclohydrolase / Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain / Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain / Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain / Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain / Aminoacid dehydrogenase-like, N-terminal domain superfamily / NAD(P)-binding domain superfamily
Similarity search - Domain/homology
Chem-9L9 / NICOTINAMIDE-ADENINE-DINUCLEOTIDE / PHOSPHATE ION / Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.12 Å
AuthorsLee, L.C. / Wu, S.Y.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2024
Title: Development of Potent and Selective Inhibitors of Methylenetetrahydrofolate Dehydrogenase 2 for Targeting Acute Myeloid Leukemia: SAR, Structural Insights, and Biological Characterization.
Authors: Chang, H.H. / Lee, L.C. / Hsu, T. / Peng, Y.H. / Huang, C.H. / Yeh, T.K. / Lu, C.T. / Huang, Z.T. / Hsueh, C.C. / Kung, F.C. / Lin, L.M. / Huang, Y.C. / Wang, Y.H. / Li, L.H. / Tang, Y.C. / ...Authors: Chang, H.H. / Lee, L.C. / Hsu, T. / Peng, Y.H. / Huang, C.H. / Yeh, T.K. / Lu, C.T. / Huang, Z.T. / Hsueh, C.C. / Kung, F.C. / Lin, L.M. / Huang, Y.C. / Wang, Y.H. / Li, L.H. / Tang, Y.C. / Chang, L. / Hsieh, C.C. / Jiaang, W.T. / Kuo, C.C. / Wu, S.Y.
History
DepositionJul 17, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 1, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
B: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,5788
Polymers69,1942
Non-polymers2,3846
Water1,60389
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)115.605, 115.605, 113.326
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65

-
Components

#1: Protein Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial


Mass: 34597.020 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MTHFD2, NMDMC / Plasmid: plasmid / Details (production host): pET14b / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P13995, methylenetetrahydrofolate dehydrogenase (NAD+), methenyltetrahydrofolate cyclohydrolase
#2: Chemical ChemComp-9L9 / (2S)-2-[[4-[[2,4-bis(azanyl)-6-oxidanylidene-1H-pyrimidin-5-yl]carbamoylamino]phenyl]carbonylamino]pentanedioic acid


Mass: 433.375 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H19N7O7 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE


Mass: 663.425 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H27N7O14P2 / Comment: NAD*YM
#4: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 89 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.16 Å3/Da / Density % sol: 61.14 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / Details: isopropanol, Bis-Tris pH 7.1, PEG 400, PEG 1000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL44XU / Wavelength: 0.9 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 25, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 2.12→30 Å / Num. obs: 48738 / % possible obs: 99.7 % / Redundancy: 4.3 % / Rmerge(I) obs: 0.061 / Net I/σ(I): 11.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2CC starRpim(I) allRrim(I) allΧ2% possible all
2.12-2.24.40.50948560.8740.9660.2770.5821.038100
2.2-2.284.40.3948790.9210.9790.2120.4451.075100
2.28-2.394.40.32648580.930.9820.1770.3731.078100
2.39-2.514.40.22548860.9710.9930.120.2561.019100
2.51-2.674.40.17148520.9830.9960.090.1941.006100
2.67-2.884.40.11648860.9930.9980.0590.131.024100
2.88-3.174.40.07248820.9960.9990.0360.0811.005100
3.17-3.624.30.05649070.9970.9990.0290.0631.044100
3.62-4.564.20.04148880.99810.0210.0461.0799.8
4.56-3040.0348440.99810.0160.0341.00797.1

-
Processing

Software
NameVersionClassification
PHENIX1.21.1_5286_000refinement
HKL-20002.3.10data scaling
HKL-20002.3.10data reduction
MOLREP11phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.12→28.9 Å / SU ML: 0.25 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 30.85 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2414 2426 4.99 %
Rwork0.2084 --
obs0.2101 48573 99.34 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.12→28.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4289 0 160 89 4538
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.007
X-RAY DIFFRACTIONf_angle_d0.931
X-RAY DIFFRACTIONf_dihedral_angle_d18.2611735
X-RAY DIFFRACTIONf_chiral_restr0.054729
X-RAY DIFFRACTIONf_plane_restr0.007785
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.12-2.160.36781400.30572656X-RAY DIFFRACTION98
2.16-2.210.3241610.28332672X-RAY DIFFRACTION100
2.21-2.260.27551670.27192694X-RAY DIFFRACTION99
2.26-2.320.24691290.26292745X-RAY DIFFRACTION99
2.32-2.380.31991550.24942692X-RAY DIFFRACTION100
2.38-2.450.28461430.24212709X-RAY DIFFRACTION100
2.45-2.530.2971260.23112747X-RAY DIFFRACTION100
2.53-2.620.2551100.22812733X-RAY DIFFRACTION100
2.62-2.720.25491520.23162696X-RAY DIFFRACTION100
2.72-2.850.27191250.23772746X-RAY DIFFRACTION100
2.85-2.990.26831380.22442760X-RAY DIFFRACTION100
3-3.180.29681300.23742730X-RAY DIFFRACTION100
3.18-3.430.28641460.22192725X-RAY DIFFRACTION100
3.43-3.770.23141430.20142742X-RAY DIFFRACTION100
3.77-4.320.21371430.18392727X-RAY DIFFRACTION100
4.32-5.430.20171660.16932728X-RAY DIFFRACTION100
5.43-28.90.19581520.18182645X-RAY DIFFRACTION95

+
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