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Yorodumi- PDB-7o2e: Crystal structure of the human METTL3-METTL14 complex bound to Co... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7o2e | ||||||
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Title | Crystal structure of the human METTL3-METTL14 complex bound to Compound 21 (ADO_AD_089) | ||||||
Components |
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Keywords | TRANSFERASE / METTL3 / Inhibitor / complex | ||||||
Function / homology | Function and homology information negative regulation of hematopoietic progenitor cell differentiation / mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity / mRNA m6A methyltransferase / mRNA m(6)A methyltransferase activity / RNA N6-methyladenosine methyltransferase complex / positive regulation of cap-independent translational initiation / RNA methyltransferase activity / mRNA modification / endothelial to hematopoietic transition / RNA methylation ...negative regulation of hematopoietic progenitor cell differentiation / mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity / mRNA m6A methyltransferase / mRNA m(6)A methyltransferase activity / RNA N6-methyladenosine methyltransferase complex / positive regulation of cap-independent translational initiation / RNA methyltransferase activity / mRNA modification / endothelial to hematopoietic transition / RNA methylation / regulation of meiotic cell cycle / primary miRNA processing / dosage compensation by inactivation of X chromosome / forebrain radial glial cell differentiation / gliogenesis / S-adenosyl-L-methionine binding / mRNA stabilization / regulation of hematopoietic stem cell differentiation / regulation of neuron differentiation / regulation of T cell differentiation / negative regulation of type I interferon-mediated signaling pathway / stem cell population maintenance / oogenesis / mRNA destabilization / negative regulation of Notch signaling pathway / mRNA catabolic process / Processing of Capped Intron-Containing Pre-mRNA / positive regulation of translation / circadian rhythm / mRNA splicing, via spliceosome / mRNA processing / cellular response to UV / spermatogenesis / nuclear body / nuclear speck / protein heterodimerization activity / innate immune response / mRNA binding / DNA damage response / Golgi apparatus / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Bedi, R.K. / Dolbois, A. / Caflisch, A. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: 1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors. Authors: Dolbois, A. / Bedi, R.K. / Bochenkova, E. / Muller, A. / Moroz-Omori, E.V. / Huang, D. / Caflisch, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7o2e.cif.gz | 126.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7o2e.ent.gz | 76.2 KB | Display | PDB format |
PDBx/mmJSON format | 7o2e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7o2e_validation.pdf.gz | 330.8 KB | Display | wwPDB validaton report |
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Full document | 7o2e_full_validation.pdf.gz | 337.8 KB | Display | |
Data in XML | 7o2e_validation.xml.gz | 11.2 KB | Display | |
Data in CIF | 7o2e_validation.cif.gz | 16.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o2/7o2e ftp://data.pdbj.org/pub/pdb/validation_reports/o2/7o2e | HTTPS FTP |
-Related structure data
Related structure data | 7o08C 7o09C 7o0lC 7o29C 7o2fC 7acdS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 28144.080 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: METTL3, MTA70 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q86U44, mRNA m6A methyltransferase |
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#2: Protein | Mass: 33621.246 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: METTL14, KIAA1627 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9HCE5 |
#3: Chemical | ChemComp-UZH / |
#4: Chemical | ChemComp-ACT / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.15 Å3/Da / Density % sol: 42.66 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / Details: 20% PEG 3350, 400mM Mg acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Dec 5, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→45 Å / Num. obs: 19442 / % possible obs: 99.9 % / Redundancy: 8.14 % / Biso Wilson estimate: 61.55 Å2 / CC1/2: 0.999 / Net I/σ(I): 17.13 |
Reflection shell | Resolution: 2.5→2.65 Å / Num. unique obs: 3082 / CC1/2: 0.496 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7ACD Resolution: 2.5→44.52 Å / SU ML: 0.3753 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 28.0876 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 62.27 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.5→44.52 Å
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Refine LS restraints |
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LS refinement shell |
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