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Yorodumi- PDB-6r8r: Structure of the Wnt deacylase Notum in complex with isoquinoline 45 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6r8r | |||||||||
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Title | Structure of the Wnt deacylase Notum in complex with isoquinoline 45 | |||||||||
Components | Palmitoleoyl-protein carboxylesterase NOTUM | |||||||||
Keywords | HYDROLASE / Wnt signalling / NOTUM Inhibitor / Crystallographic Fragment Screen | |||||||||
Function / homology | Function and homology information [Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / phospholipase C activity / Release of Hh-Np from the secreting cell / regulation of bone mineralization / negative regulation of Wnt signaling pathway / Post-translational protein phosphorylation / bone development / negative regulation of canonical Wnt signaling pathway ...[Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / phospholipase C activity / Release of Hh-Np from the secreting cell / regulation of bone mineralization / negative regulation of Wnt signaling pathway / Post-translational protein phosphorylation / bone development / negative regulation of canonical Wnt signaling pathway / Wnt signaling pathway / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / endoplasmic reticulum lumen / extracellular region Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.27 Å | |||||||||
Authors | Vecchia, L. / Zhao, Y. / Ruza, R.R. / Jones, E.Y. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Medchemcomm / Year: 2019 Title: Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen. Authors: Atkinson, B.N. / Steadman, D. / Zhao, Y. / Sipthorp, J. / Vecchia, L. / Ruza, R.R. / Jeganathan, F. / Lines, G. / Frew, S. / Monaghan, A. / Kjær, S. / Bictash, M. / Jones, E.Y. / Fish, P.V. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6r8r.cif.gz | 176.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6r8r.ent.gz | 136.8 KB | Display | PDB format |
PDBx/mmJSON format | 6r8r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r8/6r8r ftp://data.pdbj.org/pub/pdb/validation_reports/r8/6r8r | HTTPS FTP |
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-Related structure data
Related structure data | 6r8pC 6r8qC 4uz1S 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
-Protein / Sugars , 2 types, 2 molecules A
#1: Protein | Mass: 43567.148 Da / Num. of mol.: 1 / Mutation: C330S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NOTUM, OK/SW-CL.30 / Cell line (production host): HEK293S GNTI- / Production host: Homo sapiens (human) References: UniProt: Q6P988, [Wnt protein] O-palmitoleoyl-L-serine hydrolase |
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#2: Sugar | ChemComp-NAG / |
-Non-polymers , 5 types, 207 molecules
#3: Chemical | ChemComp-JV8 / ~{ | ||||||
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#4: Chemical | ChemComp-SO4 / #5: Chemical | ChemComp-DMS / #6: Chemical | ChemComp-EDO / #7: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.94 Å3/Da / Density % sol: 36.6 % |
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Crystal grow | Temperature: 300 K / Method: vapor diffusion, sitting drop / pH: 4 / Details: 1.4 M ammonium sulphate, 0.1 M citric acid, pH 4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.91587 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 5, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91587 Å / Relative weight: 1 |
Reflection | Resolution: 1.27→24.2 Å / Num. obs: 90021 / % possible obs: 100 % / Redundancy: 13 % / Biso Wilson estimate: 16.41 Å2 / CC1/2: 0.9994 / Net I/σ(I): 13.66 |
Reflection shell | Resolution: 1.27→1.29 Å / Num. unique obs: 4441 / CC1/2: 0.5197 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4UZ1 Resolution: 1.27→24.2 Å / SU ML: 0.15 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 17.31
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 79.52 Å2 / Biso mean: 23.2508 Å2 / Biso min: 11.47 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.27→24.2 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30 / % reflection obs: 100 %
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