[English] 日本語
Yorodumi
- PDB-8it9: Co-crystal structure of FTO bound to 22 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8it9
TitleCo-crystal structure of FTO bound to 22
ComponentsAlpha-ketoglutarate-dependent dioxygenase FTO
KeywordsPROTEIN BINDING / RNA demethylase / RNA binding protein
Function / homology
Function and homology information


regulation of white fat cell proliferation / tRNA demethylase activity / Reversal of alkylation damage by DNA dioxygenases / mRNA N6-methyladenine demethylase / mRNA N6-methyladenosine dioxygenase activity / regulation of respiratory system process / regulation of lipid storage / : / regulation of brown fat cell differentiation / : ...regulation of white fat cell proliferation / tRNA demethylase activity / Reversal of alkylation damage by DNA dioxygenases / mRNA N6-methyladenine demethylase / mRNA N6-methyladenosine dioxygenase activity / regulation of respiratory system process / regulation of lipid storage / : / regulation of brown fat cell differentiation / : / : / oxidative RNA demethylase activity / broad specificity oxidative DNA demethylase activity / RNA repair / Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor / DNA alkylation repair / oxidative demethylation / DNA demethylation / temperature homeostasis / mRNA destabilization / regulation of multicellular organism growth / adipose tissue development / ferrous iron binding / transferase activity / nuclear speck / intracellular membrane-bounded organelle / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Alpha-ketoglutarate-dependent dioxygenase FTO, C-terminal / Alpha-ketoglutarate-dependent dioxygenase FTO, catalytic domain / Alpha-ketoglutarate-dependent dioxygenase FTO / FTO, C-terminal domain superfamily / FTO catalytic domain / FTO C-terminal domain / FTO catalytic domain / Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily
Similarity search - Domain/homology
2-OXOGLUTARIC ACID / : / Alpha-ketoglutarate-dependent dioxygenase FTO
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.14 Å
AuthorsYang, C.-G. / Gan, J.H.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)21725801 China
National Key Research and Development Program of China2022YFC2705005 China
CitationJournal: J.Med.Chem. / Year: 2023
Title: Rational Design of RNA Demethylase FTO Inhibitors with Enhanced Antileukemia Drug-Like Properties.
Authors: Xiao, P. / Duan, Z. / Liu, Z. / Chen, L. / Zhang, D. / Liu, L. / Zhou, C. / Gan, J. / Dong, Z. / Yang, C.G.
History
DepositionMar 22, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Feb 14, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-ketoglutarate-dependent dioxygenase FTO
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,0663
Polymers56,4611
Non-polymers6062
Water1,40578
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: assay for oligomerization
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)142.189, 142.189, 84.358
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

#1: Protein Alpha-ketoglutarate-dependent dioxygenase FTO / Fat mass and obesity-associated protein / U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)- ...Fat mass and obesity-associated protein / U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO / U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO / mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO / m6A(m)-demethylase FTO / mRNA N(6)-methyladenosine demethylase FTO / tRNA N1-methyl adenine demethylase FTO


Mass: 56460.641 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FTO, KIAA1752 / Production host: Escherichia coli (E. coli)
References: UniProt: Q9C0B1, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen ...References: UniProt: Q9C0B1, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor, mRNA N6-methyladenine demethylase
#2: Chemical ChemComp-ZL6 / 2-[(2,6-diethyl-4-pyridin-4-yl-phenyl)amino]-6-(1,4-oxazepan-4-ylmethyl)benzoic acid


Mass: 459.580 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H33N3O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-AKG / 2-OXOGLUTARIC ACID / Α-Ketoglutaric acid


Mass: 146.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H6O5
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 78 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.91 Å3/Da / Density % sol: 57.68 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 100 mM sodium citrate, pH 5.4, 11.5% (w/v) polyethylene glycol (PEG) 3350, and 8% isopropanol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 0.9792 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 27, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.14→71.09 Å / Num. obs: 34944 / % possible obs: 99.1 % / Redundancy: 3.6 % / Rmerge(I) obs: 0.061 / Net I/σ(I): 10.5
Reflection shellResolution: 2.14→2.25 Å / Rmerge(I) obs: 0.386 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 5181 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.8.0158refinement
HKL-2000data scaling
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.14→71.09 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.939 / SU B: 5.174 / SU ML: 0.132 / Cross valid method: THROUGHOUT / ESU R: 0.207 / ESU R Free: 0.17 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2392 1614 4.6 %RANDOM
Rwork0.22159 ---
obs0.22243 33131 99.04 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 41.946 Å2
Baniso -1Baniso -2Baniso -3
1--0.13 Å2-0.06 Å20 Å2
2---0.13 Å20 Å2
3---0.41 Å2
Refinement stepCycle: 1 / Resolution: 2.14→71.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3386 0 44 78 3508
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0193519
X-RAY DIFFRACTIONr_bond_other_d0.0020.023084
X-RAY DIFFRACTIONr_angle_refined_deg1.0751.9574795
X-RAY DIFFRACTIONr_angle_other_deg0.89437122
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6725432
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.41924.233163
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.94915541
X-RAY DIFFRACTIONr_dihedral_angle_4_deg10.2131520
X-RAY DIFFRACTIONr_chiral_restr0.0570.2527
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0213951
X-RAY DIFFRACTIONr_gen_planes_other0.0060.02733
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.9934.4651734
X-RAY DIFFRACTIONr_mcbond_other0.9934.4641733
X-RAY DIFFRACTIONr_mcangle_it1.7676.6822161
X-RAY DIFFRACTIONr_mcangle_other1.7676.6832162
X-RAY DIFFRACTIONr_scbond_it0.7634.3831785
X-RAY DIFFRACTIONr_scbond_other0.764.3811781
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other1.3276.5662630
X-RAY DIFFRACTIONr_long_range_B_refined3.40751.0693880
X-RAY DIFFRACTIONr_long_range_B_other3.40651.0683880
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.14→2.196 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.319 91 -
Rwork0.27 2469 -
obs--99.96 %

+
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