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Yorodumi- PDB-8k72: Factor-inhibiting hypoxia-inducible factor in complex with Zn(II)... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k72 | |||||||||
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Title | Factor-inhibiting hypoxia-inducible factor in complex with Zn(II) and 2-(3-hydroxy-2-((3-(phenylsulfonamido)propanoyl)imino)-2,3-dihydrothiazol-4-yl)acetic acid | |||||||||
Components | Hypoxia-inducible factor 1-alpha inhibitor | |||||||||
Keywords | OXIDOREDUCTASE / factor-inhibiting hypoxia-inducible factor / FIH / 2OG dependent dioxygenase | |||||||||
Function / homology | Function and homology information hypoxia-inducible factor-asparagine dioxygenase / : / [protein]-asparagine 3-dioxygenase activity / peptidyl-histidine dioxygenase activity / peptidyl-aspartic acid 3-dioxygenase activity / Cellular response to hypoxia / carboxylic acid binding / positive regulation of vasculogenesis / ankyrin repeat binding / oxygen sensor activity ...hypoxia-inducible factor-asparagine dioxygenase / : / [protein]-asparagine 3-dioxygenase activity / peptidyl-histidine dioxygenase activity / peptidyl-aspartic acid 3-dioxygenase activity / Cellular response to hypoxia / carboxylic acid binding / positive regulation of vasculogenesis / ankyrin repeat binding / oxygen sensor activity / Notch binding / negative regulation of Notch signaling pathway / NF-kappaB binding / positive regulation of myoblast differentiation / ferrous iron binding / transcription corepressor activity / perinuclear region of cytoplasm / protein homodimerization activity / zinc ion binding / nucleoplasm / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.45 Å | |||||||||
Authors | Nakashima, Y. / Corner, T.P. / Teo, R.Z.R. / Brewitz, L. / Schofield, C.J. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Chem Sci / Year: 2023 Title: Structure-guided optimisation of N -hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-alpha. Authors: Corner, T.P. / Teo, R.Z.R. / Wu, Y. / Salah, E. / Nakashima, Y. / Fiorini, G. / Tumber, A. / Brasnett, A. / Holt-Martyn, J.P. / Figg Jr., W.D. / Zhang, X. / Brewitz, L. / Schofield, C.J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8k72.cif.gz | 190.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k72.ent.gz | 127.4 KB | Display | PDB format |
PDBx/mmJSON format | 8k72.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k72_validation.pdf.gz | 760 KB | Display | wwPDB validaton report |
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Full document | 8k72_full_validation.pdf.gz | 762.5 KB | Display | |
Data in XML | 8k72_validation.xml.gz | 15.7 KB | Display | |
Data in CIF | 8k72_validation.cif.gz | 21.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k7/8k72 ftp://data.pdbj.org/pub/pdb/validation_reports/k7/8k72 | HTTPS FTP |
-Related structure data
Related structure data | 8k71C 8k73C 4b7kS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 40328.281 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HIF1AN, FIH1 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one ...References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, 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 |
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-Non-polymers , 5 types, 83 molecules
#2: Chemical | ChemComp-SO4 / #3: Chemical | #4: Chemical | ChemComp-ZN / | #5: Chemical | ChemComp-VJF / | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.37 Å3/Da / Density % sol: 63.53 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 0.27 mM FIH, 0.5 mM zinc acetate, 2 mM TC167, 0.1 M HEPES, pH 7.5, 6%w/v PEG400, 1.6 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 20, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97625 Å / Relative weight: 1 |
Reflection | Resolution: 2.45→72.53 Å / Num. obs: 21056 / % possible obs: 100 % / Redundancy: 26.5 % / Biso Wilson estimate: 72.14 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.168 / Net I/σ(I): 15.1 |
Reflection shell | Resolution: 2.45→2.49 Å / Redundancy: 25.6 % / Rmerge(I) obs: 5.078 / Mean I/σ(I) obs: 0.6 / Num. unique obs: 1039 / CC1/2: 0.533 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4B7K Resolution: 2.45→61.24 Å / SU ML: 0.372 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 30.2521 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: 92.83 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.45→61.24 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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