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Yorodumi- PDB-4x6i: Development of N-(Functionalized benzoyl)-homocycloleucyl-glycino... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4x6i | ||||||
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Title | Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors. | ||||||
Components | Cathepsin K | ||||||
Keywords | HYDROLASE / cathepsin K / inhibitor | ||||||
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 / fibronectin binding / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / bone resorption / cysteine-type peptidase activity / cellular response to transforming growth factor beta stimulus / collagen binding / MHC class II antigen presentation / Degradation of the extracellular matrix / lysosomal lumen / proteolysis involved in protein catabolic process / positive regulation of apoptotic signaling pathway / 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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.87 Å | ||||||
Authors | Borisek, J. / Mohar, B. / Vizovisek, M. / Sosnowski, P. / Turk, D. / Turk, B. / Novic, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors. Authors: Borisek, J. / Vizovisek, M. / Sosnowski, P. / Turk, B. / Turk, D. / Mohar, B. / Novic, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4x6i.cif.gz | 61.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4x6i.ent.gz | 43 KB | Display | PDB format |
PDBx/mmJSON format | 4x6i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x6/4x6i ftp://data.pdbj.org/pub/pdb/validation_reports/x6/4x6i | HTTPS FTP |
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-Related structure data
Related structure data | 4x6hC 4x6jC 1atkS 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
#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) / Gene: CTSK, CTSO, CTSO2 / Production host: Komagataella pastoris GS115 (fungus) / References: UniProt: P43235, cathepsin K | ||
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#2: Chemical | ChemComp-3Y1 / | ||
#3: Chemical | ChemComp-SO4 / #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: 1.85 Å3/Da / Density % sol: 33.65 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop Details: Lithium sulfate 0.2M, Sodium acetate 0.1M, Peg 8000 30% |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: BRUKER AXS MICROSTAR / Wavelength: 1.54184 Å |
Detector | Type: Bruker Platinum 135 / Detector: CCD / Date: Jan 5, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54184 Å / Relative weight: 1 |
Reflection | Resolution: 1.87→46.28 Å / Num. obs: 14804 / % possible obs: 98.31 % / Redundancy: 9.5 % / Rmerge(I) obs: 0.2593 / Net I/σ(I): 9.96 |
Reflection shell | Resolution: 1.87→1.937 Å / Redundancy: 7.4 % / Rmerge(I) obs: 0.9815 / % possible all: 98.16 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1ATK Resolution: 1.87→46.28 Å / Cor.coef. Fo:Fc: 0.931 / Cor.coef. Fo:Fc free: 0.888 / WRfactor Rfree: 0.1988 / WRfactor Rwork: 0.1549 / FOM work R set: 0.8063 / SU B: 4.162 / SU ML: 0.12 / SU R Cruickshank DPI: 0.1887 / SU Rfree: 0.1671 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.189 / ESU R Free: 0.167 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 36.95 Å2 / Biso mean: 8.629 Å2 / Biso min: 2 Å2
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Refinement step | Cycle: final / Resolution: 1.87→46.28 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.87→1.919 Å / Total num. of bins used: 20
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