+Open data
-Basic information
Entry | Database: PDB / ID: 7pkv | ||||||
---|---|---|---|---|---|---|---|
Title | Notum_Inhibitor ARUK3000223 | ||||||
Components | Palmitoleoyl-protein carboxylesterase NOTUM | ||||||
Keywords | HYDROLASE / Notum Inhibitor | ||||||
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: 1.68 Å | ||||||
Authors | Ruza, R. / Zhao, Y. / Fish, P. / Jones, E.Y. | ||||||
Funding support | United Kingdom, 1items
| ||||||
Citation | Journal: J.Med.Chem. / Year: 2022 Title: Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit. Authors: Willis, N.J. / Mahy, W. / Sipthorp, J. / Zhao, Y. / Woodward, H.L. / Atkinson, B.N. / Bayle, E.D. / Svensson, F. / Frew, S. / Jeganathan, F. / Monaghan, A. / Benvegnu, S. / Jolly, S. / ...Authors: Willis, N.J. / Mahy, W. / Sipthorp, J. / Zhao, Y. / Woodward, H.L. / Atkinson, B.N. / Bayle, E.D. / Svensson, F. / Frew, S. / Jeganathan, F. / Monaghan, A. / Benvegnu, S. / Jolly, S. / Vecchia, L. / Ruza, R.R. / Kjaer, S. / Howell, S. / Snijders, A.P. / Bictash, M. / Salinas, P.C. / Vincent, J.P. / Jones, E.Y. / Whiting, P. / Fish, P.V. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7pkv.cif.gz | 89.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7pkv.ent.gz | 64.6 KB | Display | PDB format |
PDBx/mmJSON format | 7pkv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pk/7pkv ftp://data.pdbj.org/pub/pdb/validation_reports/pk/7pkv | HTTPS FTP |
---|
-Related structure data
Related structure data | 7pjrC 7pk3C 6r8pS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
-Protein / Sugars , 2 types, 2 molecules A
#1: Protein | Mass: 43567.148 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NOTUM, OK/SW-CL.30 / Cell line (production host): Hek 293S GNTI- / Production host: Homo sapiens (human) References: UniProt: Q6P988, [Wnt protein] O-palmitoleoyl-L-serine hydrolase |
---|---|
#3: Sugar | ChemComp-NAG / |
-Non-polymers , 4 types, 92 molecules
#2: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-DMS / | #5: Chemical | ChemComp-63Z / [ | #6: Water | ChemComp-HOH / | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 1.95 Å3/Da / Density % sol: 36.99 % |
---|---|
Crystal grow | Temperature: 296 K / Method: vapor diffusion, sitting drop / pH: 4.2 Details: 1.5 M Ammonium Sulphate 0.1 M Sodium Citrate, pH4.2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.91587 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 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: 1.68→47.8 Å / Num. obs: 39638 / % possible obs: 100 % / Redundancy: 13 % / CC1/2: 1 / Net I/σ(I): 15.2 |
Reflection shell | Resolution: 1.68→1.71 Å / Num. unique obs: 1964 / CC1/2: 0.507 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6R8P Resolution: 1.68→47.8 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 22.39 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 162.7 Å2 / Biso mean: 33.7745 Å2 / Biso min: 17.83 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.68→47.8 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14 / % reflection obs: 100 %
|