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Yorodumi- PDB-8ixs: Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1/Nr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ixs | ||||||
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Title | Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1/Nrf2 PPI Inhibitor for Treatment of Chronic Kidney Disease | ||||||
Components | Kelch-like ECH-associated protein 1 | ||||||
Keywords | PEPTIDE BINDING PROTEIN / chronic kidney disease (CKD) / Keap1 / Nrf2 / non-covalent inhibitor | ||||||
Function / homology | Function and homology information negative regulation of response to oxidative stress / regulation of epidermal cell differentiation / Nuclear events mediated by NFE2L2 / Cul3-RING ubiquitin ligase complex / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity / cellular response to interleukin-4 / inclusion body / regulation of autophagy / actin filament ...negative regulation of response to oxidative stress / regulation of epidermal cell differentiation / Nuclear events mediated by NFE2L2 / Cul3-RING ubiquitin ligase complex / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity / cellular response to interleukin-4 / inclusion body / regulation of autophagy / actin filament / negative regulation of DNA-binding transcription factor activity / KEAP1-NFE2L2 pathway / disordered domain specific binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Neddylation / cellular response to oxidative stress / midbody / ubiquitin-dependent protein catabolic process / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / endoplasmic reticulum / nucleoplasm / identical protein binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.48 Å | ||||||
Authors | Nomura, A. / Yamaguchi, K. / Adachi, T. | ||||||
Funding support | 1items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2023 Title: Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1-Nrf2 PPI Inhibitor. Authors: Otake, K. / Ubukata, M. / Nagahashi, N. / Ogawa, N. / Hantani, Y. / Hantani, R. / Adachi, T. / Nomura, A. / Yamaguchi, K. / Maekawa, M. / Mamada, H. / Motomura, T. / Sato, M. / Harada, K. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ixs.cif.gz | 165.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ixs.ent.gz | 107.8 KB | Display | PDB format |
PDBx/mmJSON format | 8ixs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ix/8ixs ftp://data.pdbj.org/pub/pdb/validation_reports/ix/8ixs | HTTPS FTP |
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-Related structure data
Related structure data | 8ivgC 8ivrC 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: 34730.027 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Escherichia coli (E. coli) / References: UniProt: Q14145 | ||||
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#2: Chemical | ChemComp-T6I / ( | ||||
#3: Chemical | ChemComp-SO4 / #4: 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: 2.46 Å3/Da / Density % sol: 50.03 % |
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Crystal grow | Temperature: 278 K / Method: vapor diffusion / pH: 7.5 Details: 6-10mg/mL and crystallized with the solution with 0.1M Na acetate (pH5.0) and 1.5M di-ammonium sulfate or the solution with 0.1M Na acetate (pH5.0), 1.5M di-ammonium, and 0.1-0.15M NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jul 15, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.48→89.71 Å / Num. obs: 56260 / % possible obs: 99.5 % / Redundancy: 29.2 % / Rmerge(I) obs: 0.092 / Rpim(I) all: 0.017 / Rrim(I) all: 0.093 / Net I/σ(I): 3.9 |
Reflection shell | Resolution: 1.48→1.52 Å / Redundancy: 19.8 % / Rmerge(I) obs: 0.913 / Mean I/σ(I) obs: 3.9 / Num. unique obs: 3884 / CC1/2: 0.903 / Rpim(I) all: 0.193 / Rrim(I) all: 0.935 / % possible all: 93.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.48→89.71 Å / SU ML: 0.1522 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 17.5353 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 21.83 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.48→89.71 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 23.045 Å / Origin y: 61.625 Å / Origin z: 38.401 Å
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Refinement TLS group |
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