+Open data
-Basic information
Entry | Database: PDB / ID: 7ofd | ||||||
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Title | Keap1 kelch domain bound to a small molecule fragment | ||||||
Components | Kelch-like ECH-associated protein 1 | ||||||
Keywords | PEPTIDE BINDING PROTEIN / Keap1 / Nrf2 / Oxidative stress / Small molecule complex / Maybridge | ||||||
Function / homology | Function and homology information cellular response to carbohydrate stimulus / KEAP1-NFE2L2 pathway / regulation of epidermal cell differentiation / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / Ub-specific processing proteases / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / ubiquitin-like ligase-substrate adaptor activity / centriolar satellite ...cellular response to carbohydrate stimulus / KEAP1-NFE2L2 pathway / regulation of epidermal cell differentiation / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / Ub-specific processing proteases / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / ubiquitin-like ligase-substrate adaptor activity / centriolar satellite / cellular response to interleukin-4 / inclusion body / regulation of autophagy / actin filament / adherens junction / disordered domain specific binding / midbody / cellular response to oxidative stress / ubiquitin-dependent protein catabolic process / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / protein ubiquitination / negative regulation of gene expression / focal adhesion / regulation of DNA-templated transcription / endoplasmic reticulum / protein-containing complex / nucleoplasm / identical protein binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.25 Å | ||||||
Authors | Narayanan, D. / Bach, A. / Gajhede, M. | ||||||
Funding support | Denmark, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Development of Noncovalent Small-Molecule Keap1-Nrf2 Inhibitors by Fragment-Based Drug Discovery. Authors: Narayanan, D. / Tran, K.T. / Pallesen, J.S. / Solbak, S.M.O. / Qin, Y. / Mukminova, E. / Luchini, M. / Vasilyeva, K.O. / Gonzalez Chichon, D. / Goutsiou, G. / Poulsen, C. / Haapanen, N. / ...Authors: Narayanan, D. / Tran, K.T. / Pallesen, J.S. / Solbak, S.M.O. / Qin, Y. / Mukminova, E. / Luchini, M. / Vasilyeva, K.O. / Gonzalez Chichon, D. / Goutsiou, G. / Poulsen, C. / Haapanen, N. / Popowicz, G.M. / Sattler, M. / Olagnier, D. / Gajhede, M. / Bach, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ofd.cif.gz | 221.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ofd.ent.gz | 148.4 KB | Display | PDB format |
PDBx/mmJSON format | 7ofd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ofd_validation.pdf.gz | 763.7 KB | Display | wwPDB validaton report |
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Full document | 7ofd_full_validation.pdf.gz | 764.6 KB | Display | |
Data in XML | 7ofd_validation.xml.gz | 14.3 KB | Display | |
Data in CIF | 7ofd_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/of/7ofd ftp://data.pdbj.org/pub/pdb/validation_reports/of/7ofd | HTTPS FTP |
-Related structure data
Related structure data | 7of8C 7of9C 7ofaC 7ofbC 7ofcC 7ofeC 7offC 5fnuS 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: 33362.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Keap1, Inrf2, Kiaa0132 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q9Z2X8 | ||||||||
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#2: Chemical | #3: Chemical | ChemComp-DMS / #4: Chemical | ChemComp-VBW / | #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: 2.46 Å3/Da / Density meas: 50.1 Mg/m3 / Density % sol: 51.32 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 0.5 M Ammonium sulfate, 0.1 M Sodium citrate tribasic dihydrate pH 5.6 and 1.0 M Lithium sulfate monohydrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 0.976246 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 26, 2019 / Details: KB mirrors |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976246 Å / Relative weight: 1 |
Reflection | Resolution: 1.249→51.51 Å / Num. obs: 91534 / % possible obs: 99.23 % / Redundancy: 18.2 % / Biso Wilson estimate: 14.23 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.06059 / Rpim(I) all: 0.01388 / Rrim(I) all: 0.06219 / Net I/σ(I): 24.73 |
Reflection shell | Resolution: 1.249→1.294 Å / Redundancy: 8.6 % / Rmerge(I) obs: 0.5983 / Mean I/σ(I) obs: 2.45 / Num. unique obs: 8560 / CC1/2: 0.875 / CC star: 0.966 / Rpim(I) all: 0.2149 / Rrim(I) all: 0.6375 / % possible all: 93.34 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5FNU Resolution: 1.25→51.51 Å / SU ML: 0.121 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 15.6728 / Stereochemistry target values: GeoStd + Monomer Library
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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: 20.64 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.25→51.51 Å
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Refine LS restraints |
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LS refinement shell |
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