[English] 日本語
Yorodumi
- PDB-7e8z: Crystal structure of the human fat mass and obesity associated pr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7e8z
TitleCrystal structure of the human fat mass and obesity associated protein (FTO) in complex with SS81
ComponentsAlpha-ketoglutarate-dependent dioxygenase FTO
KeywordsOXIDOREDUCTASE / Double-stranded beta helix / 2OG and Fe(II)-dependent oxygenase / RNA demethylase
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
Chem-HZX / Alpha-ketoglutarate-dependent dioxygenase FTO
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.55 Å
AuthorsTam, N.Y. / Ng, Y.M. / Shishodia, S. / McDonough, M.A. / Schofield, C.J. / Aik, W.S.
Funding support Hong Kong, 1items
OrganizationGrant numberCountry
The University Grants Committee, Research Grants Council (RGC)22301719 Hong Kong
CitationJournal: J.Med.Chem. / Year: 2021
Title: Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors.
Authors: Shishodia, S. / Demetriades, M. / Zhang, D. / Tam, N.Y. / Maheswaran, P. / Clunie-O'Connor, C. / Tumber, A. / Leung, I.K.H. / Ng, Y.M. / Leissing, T.M. / El-Sagheer, A.H. / Salah, E. / ...Authors: Shishodia, S. / Demetriades, M. / Zhang, D. / Tam, N.Y. / Maheswaran, P. / Clunie-O'Connor, C. / Tumber, A. / Leung, I.K.H. / Ng, Y.M. / Leissing, T.M. / El-Sagheer, A.H. / Salah, E. / Brown, T. / Aik, W.S. / McDonough, M.A. / Schofield, C.J.
History
DepositionMar 3, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 13, 2021Provider: repository / Type: Initial release
Revision 1.1Feb 2, 2022Group: 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.identifier_ORCID
Revision 1.2Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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)57,2213
Polymers56,8231
Non-polymers3982
Water21612
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area100 Å2
ΔGint-39 kcal/mol
Surface area19880 Å2
Unit cell
Length a, b, c (Å)142.293, 142.293, 83.901
Angle α, β, γ (deg.)90.000, 90.000, 120.000
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: 56823.047 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-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-HZX / 2-[[6-[(4-nitrophenyl)amino]-3-oxidanyl-pyridin-2-yl]carbonylamino]ethanoic acid


Mass: 332.268 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H12N4O6 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 12 / 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: 2.88 Å3/Da / Density % sol: 57.24 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6
Details: 13.5% PEG3350, 100 mM trisodium citrate pH 5.6, 4% tert-butanol, 1 mM NADH

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9999 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Dec 24, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 2.55→71.14 Å / Num. obs: 20599 / % possible obs: 99.84 % / Redundancy: 3.18 % / Biso Wilson estimate: 61.9 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.087 / Rpim(I) all: 0.06 / Rrim(I) all: 0.106 / Net I/σ(I): 10.4
Reflection shellResolution: 2.55→2.59 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.766 / Mean I/σ(I) obs: 0.5 / Num. unique obs: 1000 / CC1/2: 0.57 / Rpim(I) all: 0.514 / Rrim(I) all: 0.927 / % possible all: 99.8

-
Processing

Software
NameVersionClassification
DIALSdata scaling
PHENIX1.18.2_3874refinement
PDB_EXTRACT3.27data extraction
DIALSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4IE5

4ie5


Resolution: 2.55→41.08 Å / SU ML: 0.41 / Cross valid method: THROUGHOUT / σ(F): 1.96 / Phase error: 28.44 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.237 937 4.59 %
Rwork0.1954 19491 -
obs0.1971 20428 98.92 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 181.14 Å2 / Biso mean: 84.8688 Å2 / Biso min: 40.87 Å2
Refinement stepCycle: final / Resolution: 2.55→41.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3420 0 25 12 3457
Biso mean--75.06 66.59 -
Num. residues----441
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 7

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.55-2.680.33151570.3312621277895
2.68-2.850.34051030.26892793289699
2.85-3.070.29771680.26332782295099
3.07-3.380.29231740.254227782952100
3.38-3.870.22421200.199728222942100
3.87-4.870.216840.163828792963100
4.87-41.080.18841310.163428162947100
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)
16.070.92292.76434.06310.46163.82010.15020.6819-0.8023-0.25930.13130.22930.3110.1698-0.34470.5168-0.0562-0.00450.453-0.07550.6604-12.977-33.8872-35.89
25.69880.55443.90897.67270.34324.3220.04251.199-0.5429-0.31320.2853-0.75770.14610.8843-0.16180.4393-0.0382-0.03880.7129-0.13950.69164.758-27.781-31.7359
35.66982.25531.63512.33580.75911.68930.2357-0.0453-0.30980.218-0.0503-0.14880.19070.1811-0.17140.48320.0084-0.01820.46020.07420.4691.8403-22.3468-23.8812
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 27 through 91 )A27 - 91
2X-RAY DIFFRACTION2chain 'A' and (resid 92 through 129 )A92 - 129
3X-RAY DIFFRACTION3chain 'A' and (resid 130 through 503 )A130 - 503

+
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