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Yorodumi- PDB-8ihz: FACTOR INHIBITING HIF-1 ALPHA in complex with (5-(1-(3-(4-chlorop... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ihz | |||||||||
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Title | FACTOR INHIBITING HIF-1 ALPHA in complex with (5-(1-(3-(4-chlorophenyl)propyl)-1H-1,2,3-triazol-4-yl)-3-hydroxypicolinoyl)glycine | |||||||||
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 / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.22 Å | |||||||||
Authors | Nakashima, Y. / Corner, T. / Zhang, X. / Schofield, C.J. | |||||||||
Funding support | China, United Kingdom, 2items
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Citation | Journal: Angew.Chem.Int.Ed.Engl. / Year: 2024 Title: A Small-Molecule Inhibitor of Factor Inhibiting HIF Binding to a Tyrosine-flip Pocket for the Treatment of Obesity. Authors: Wu, Y. / Chen, Y. / Corner, T. / Nakashima, Y. / Salah, E. / Li, Z. / Zhang, L. / Yang, L. / Tumber, A. / Sun, Z. / Wen, Y. / Zhong, A. / Yang, F. / Li, X. / Zhang, Z. / Schofield, C. / Zhang, X. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ihz.cif.gz | 254.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ihz.ent.gz | 174.8 KB | Display | PDB format |
PDBx/mmJSON format | 8ihz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ihz_validation.pdf.gz | 718.3 KB | Display | wwPDB validaton report |
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Full document | 8ihz_full_validation.pdf.gz | 725.5 KB | Display | |
Data in XML | 8ihz_validation.xml.gz | 16.7 KB | Display | |
Data in CIF | 8ihz_validation.cif.gz | 22.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ih/8ihz ftp://data.pdbj.org/pub/pdb/validation_reports/ih/8ihz | HTTPS FTP |
-Related structure data
Related structure data | 8ii0C 1h2kS 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
#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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#2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-ZN / | #4: Chemical | ChemComp-P1X / | Mass: 415.830 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H18ClN5O4 / Feature type: SUBJECT OF INVESTIGATION #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: 3.42 Å3/Da / Density % sol: 64.05 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 1.6 M AMMONIUM SULPHATE, 6% PEG 400, 0.1 M HEPES |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97624 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Feb 4, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97624 Å / Relative weight: 1 |
Reflection | Resolution: 2.22→74.65 Å / Num. obs: 28505 / % possible obs: 100 % / Redundancy: 25.6 % / Biso Wilson estimate: 73.37 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.092 / Net I/σ(I): 20 |
Reflection shell | Resolution: 2.22→2.26 Å / Redundancy: 26.6 % / Rmerge(I) obs: 5.601 / Mean I/σ(I) obs: 0.3 / Num. unique obs: 1381 / CC1/2: 0.285 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1H2K Resolution: 2.22→61.22 Å / SU ML: 0.3589 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 29.5713 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: 96.82 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.22→61.22 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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