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Yorodumi- PDB-3kwz: Cathepsin K in complex with a non-selective 2-cyano-pyrimidine in... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3kwz | ||||||
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Title | Cathepsin K in complex with a non-selective 2-cyano-pyrimidine inhibitor | ||||||
Components | Cathepsin K | ||||||
Keywords | HYDROLASE / cathepsin K / enzyme inhibitor / covalent reversible inhibitor / Disease mutation / Disulfide bond / Glycoprotein / Lysosome / Protease / Thiol protease / Zymogen | ||||||
Function / homology | Function and homology information cathepsin K / mononuclear cell differentiation / intramembranous ossification / negative regulation of cartilage development / cellular response to zinc ion starvation / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / thyroid hormone generation / endolysosome lumen / Trafficking and processing of endosomal TLR / proteoglycan binding ...cathepsin K / mononuclear cell differentiation / intramembranous ossification / negative regulation of cartilage development / cellular response to zinc ion starvation / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / thyroid hormone generation / endolysosome lumen / Trafficking and processing of endosomal TLR / proteoglycan binding / Activation of Matrix Metalloproteinases / cysteine-type endopeptidase activator activity involved in apoptotic process / mitophagy / Collagen degradation / fibronectin binding / collagen catabolic process / extracellular matrix disassembly / cysteine-type peptidase activity / positive regulation of apoptotic signaling pathway / bone resorption / cellular response to transforming growth factor beta stimulus / collagen binding / MHC class II antigen presentation / Degradation of the extracellular matrix / proteolysis involved in protein catabolic process / lysosomal lumen / response to insulin / response to organic cyclic compound / cellular response to tumor necrosis factor / response to ethanol / lysosome / immune response / apical plasma membrane / external side of plasma membrane / cysteine-type endopeptidase activity / serine-type endopeptidase activity / intracellular membrane-bounded organelle / proteolysis / extracellular space / extracellular region / nucleoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.49 Å | ||||||
Authors | Fradera, X. / Uitdehaag, J.C.M. / van Zeeland, M. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2010 Title: Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors Authors: Rankovic, Z. / Cai, J. / Kerr, J. / Fradera, X. / Robinson, J. / Mistry, A. / Hamilton, E. / McGarry, G. / Andrews, F. / Caulfield, W. / Cumming, I. / Dempster, M. / Waller, J. / Scullion, P. ...Authors: Rankovic, Z. / Cai, J. / Kerr, J. / Fradera, X. / Robinson, J. / Mistry, A. / Hamilton, E. / McGarry, G. / Andrews, F. / Caulfield, W. / Cumming, I. / Dempster, M. / Waller, J. / Scullion, P. / Martin, I. / Mitchell, A. / Long, C. / Baugh, M. / Westwood, P. / Kinghorn, E. / Bruin, J. / Hamilton, W. / Uitdehaag, J. / van Zeeland, M. / Potin, D. / Saniere, L. / Fouquet, A. / Chevallier, F. / Deronzier, H. / Dorleans, C. / Nicolai, E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3kwz.cif.gz | 60.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3kwz.ent.gz | 44 KB | Display | PDB format |
PDBx/mmJSON format | 3kwz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kw/3kwz ftp://data.pdbj.org/pub/pdb/validation_reports/kw/3kwz | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 23523.480 Da / Num. of mol.: 1 / Fragment: UNP residues 115-329 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): ovary cells / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P43235, cathepsin K | ||||
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#2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-KWZ / | #4: 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: 2.14 Å3/Da / Density % sol: 42.45 % |
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Crystal grow | Method: vapor diffusion, hanging drop / pH: 8.4 Details: 26% PEG 4000, 0.1M Tris, 0.2M LiSO4, 15% PEG 400, pH 8.4, VAPOR DIFFUSION, HANGING DROP |
-Data collection
Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.933 Å |
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Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Dec 12, 2005 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.933 Å / Relative weight: 1 |
Reflection | Resolution: 1.49→51.23 Å / Num. all: 28061 / Num. obs: 28061 / % possible obs: 81.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 10.26 % / Biso Wilson estimate: 16.5 Å2 / Rmerge(I) obs: 0.132 / Net I/σ(I): 8 |
Reflection shell | Resolution: 1.49→1.54 Å / Redundancy: 1.78 % / Rmerge(I) obs: 0.132 / Mean I/σ(I) obs: 0.7 / % possible all: 19.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: In-house cathepsin K structure Resolution: 1.49→42.22 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.916 / SU B: 4.709 / SU ML: 0.147 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(I): 1 / ESU R: 0.121 / ESU R Free: 0.129 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 22.048 Å2
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Refinement step | Cycle: LAST / Resolution: 1.49→42.22 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.493→1.532 Å / Total num. of bins used: 20
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