[English] 日本語
Yorodumi
- PDB-4qho: Crystal structure of the human fat mass and obesity associated pr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4qho
TitleCrystal structure of the human fat mass and obesity associated protein (FTO) in complex with CCO10
ComponentsAlpha-ketoglutarate-dependent dioxygenase FTO
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / jelly-roll motif / oxidoreductase / dioxygenase / double-stranded beta helix fold / nucleic acid demethylase / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
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 / oxidative RNA demethylase activity / broad specificity oxidative DNA demethylase activity ...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 / snRNA processing / 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 / RNA repair / DNA alkylation repair / 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
FTO C-terminal domain / 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 / Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily ...FTO C-terminal domain / 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 / Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily / Methane Monooxygenase Hydroxylase; Chain G, domain 1 / Jelly Rolls / Up-down Bundle / Sandwich / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Chem-NKG / Alpha-ketoglutarate-dependent dioxygenase FTO
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.37 Å
AuthorsAik, W.S. / Clunie-O'Connor, C. / McDonough, M.A. / Schofield, C.J.
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
DepositionMay 28, 2014Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jun 3, 2015Provider: repository / Type: Initial release
Revision 1.1Oct 13, 2021Group: Database references / Derived calculations / Structure summary
Category: citation / citation_author ...citation / citation_author / database_2 / pdbx_struct_conn_angle / struct / struct_conn / struct_ref_seq_dif / struct_site
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct.title / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.2Feb 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 1.3Nov 8, 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)57,2113
Polymers56,8231
Non-polymers3882
Water50428
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)141.384, 141.384, 83.954
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


Mass: 56823.047 Da / Num. of mol.: 1 / Fragment: UNP residues 32-505
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FTO, KIAA1752 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
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
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-NKG / N-{[3-hydroxy-6-(naphthalen-1-yl)pyridin-2-yl]carbonyl}glycine


Mass: 322.315 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H14N2O4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 28 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.84 Å3/Da / Density % sol: 56.72 % / Mosaicity: 0.497 ° / Mosaicity esd: 0.004 °
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6
Details: 100mM trisodium citrate, 8% PEG 3350, 4% tert-butanol, 8mg/ml protein, 1mM ZnSO4, 1mM inhibitor, pH 5.6, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 1.2716 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Sep 25, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.2716 Å / Relative weight: 1
ReflectionResolution: 2.32→50 Å / Num. all: 26710 / Num. obs: 26707 / % possible obs: 100 % / Observed criterion σ(F): -3 / Redundancy: 7.2 % / Biso Wilson estimate: 67.42 Å2 / Rmerge(I) obs: 0.204 / Χ2: 1.226 / Net I/σ(I): 11.5
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Mean I/σ(I) obsNum. unique allΧ2% possible allRmerge(I) obs
2.32-2.44.31226970.921100
2.4-2.55.411.726480.986100
2.5-2.616.610.626841.0021000.953
2.61-2.757.111.326671.1481000.66
2.75-2.927.810.626711.2181000.426
2.92-3.157.78.726551.3431000.291
3.15-3.478.16.426691.3681000.228
3.47-3.978.24.326851.3461000.202
3.97-58.4326541.37299.90.193
5-508.6226771.2411000.192

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACT3.14data extraction
GDAdata collection
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ID 4IE5

4ie5


Resolution: 2.37→49.48 Å / Isotropic thermal model: isotropic
RfactorNum. reflection% reflectionSelection details
Rfree0.2076 1872 7.45 %random
Rwork0.1769 ---
all-26707 --
obs-25134 94.1 %-
Displacement parametersBiso max: 195.14 Å2 / Biso mean: 86.97 Å2 / Biso min: 55.24 Å2
Refinement stepCycle: LAST / Resolution: 2.37→49.48 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3408 0 25 28 3461
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONf_bond_d0.011
X-RAY DIFFRACTIONf_angle_deg1.216
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkRefine-IDNum. reflection obs% reflection obs (%)
2.3787-2.44310.32591410.2731X-RAY DIFFRACTION1919100
5.5888-40.820.1751360.1536X-RAY DIFFRACTION193499.8
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)
12.60540.88570.79233.07390.98312.85380.1773-0.10020.0560.4565-0.182-0.56570.20550.2084-0.03910.74220.0447-0.05660.7763-0.01460.851235.5107-6.1798-19.6657
23.6285-0.09020.90292.07180.74353.31250.4614-0.6475-0.4010.3451-0.2611-0.23720.5143-0.354-0.09340.7555-0.1165-0.04330.71430.03230.695523.2909-13.827-17.0833
33.62991.23351.15423.6797-0.44172.76710.35640.0186-0.08430.0111-0.2454-0.16450.27430.321-0.06880.51940.024-0.0320.5853-0.08690.602232.9021-3.7104-22.677
44.19520.85821.18772.7957-0.09873.72360.17220.3636-0.4827-0.1086-0.0801-0.14420.25910.058-0.09130.6548-0.03830.02460.6184-0.10290.61454.3142-19.5632-40.4047
53.430.83050.55092.1815-0.39361.06610.25660.6909-0.573-0.6080.0015-0.3220.36680.5269-0.20861.0561-0.00040.04511.1679-0.27860.848512.2613-21.5367-50.1674
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resseq 28:91 )A28 - 91
2X-RAY DIFFRACTION2chain 'A' and (resseq 92:162 )A92 - 162
3X-RAY DIFFRACTION3chain 'A' and (resseq 163:330 )A163 - 330
4X-RAY DIFFRACTION4chain 'A' and (resseq 331:457 )A331 - 457
5X-RAY DIFFRACTION5chain 'A' and (resseq 458:504 )A458 - 504

+
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