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Yorodumi- PDB-3c27: Cyanofluorophenylacetamides as Orally Efficacious Thrombin Inhibitors -
+Open data
-Basic information
Entry | Database: PDB / ID: 3c27 | ||||||
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Title | Cyanofluorophenylacetamides as Orally Efficacious Thrombin Inhibitors | ||||||
Components |
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Keywords | HYDROLASE/HYDROLASE INHIBITOR / Thrombin / Serine protease / Acute phase / Blood coagulation / Gamma-carboxyglutamic acid / Glycoprotein / Hydrolase / Kringle / Protease / Secreted / Zymogen / Protease inhibitor / Serine protease inhibitor / Sulfation / HYDROLASE-HYDROLASE INHIBITOR complex | ||||||
Function / homology | Function and homology information positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin ...positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of platelet activation / negative regulation of astrocyte differentiation / positive regulation of collagen biosynthetic process / negative regulation of cytokine production involved in inflammatory response / positive regulation of blood coagulation / negative regulation of fibrinolysis / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / regulation of cytosolic calcium ion concentration / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / Regulation of Complement cascade / acute-phase response / lipopolysaccharide binding / Cell surface interactions at the vascular wall / negative regulation of proteolysis / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / response to wounding / platelet activation / Golgi lumen / positive regulation of protein localization to nucleus / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of reactive oxygen species metabolic process / blood coagulation / antimicrobial humoral immune response mediated by antimicrobial peptide / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / regulation of cell shape / G alpha (q) signalling events / positive regulation of cell growth / collagen-containing extracellular matrix / blood microparticle / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / positive regulation of protein phosphorylation / endoplasmic reticulum lumen / signaling receptor binding / serine-type endopeptidase activity / calcium ion binding / positive regulation of cell population proliferation / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Hirudo medicinalis (medicinal leech) | ||||||
Method | X-RAY DIFFRACTION / Resolution: 2.182 Å | ||||||
Authors | Spurlino, J.C. / McMillan, M. / Lewandowski, F. / Milligan, C. | ||||||
Citation | Journal: To be Published Title: Cyanofluorophenylacetamides as Orally Efficacious Thrombin Inhibitors Authors: Kreuter, K.D. / Lee, L. / Lu, T. / Giardino, E.C. / Patel, S. / Haung, H. / Xu, G. / Fitzgerald, M. / Mohan, M. / Crysler, C. / Eisennagel, S. / Dasgupta, M. / McMillan, M. / Spurlino, J.C. ...Authors: Kreuter, K.D. / Lee, L. / Lu, T. / Giardino, E.C. / Patel, S. / Haung, H. / Xu, G. / Fitzgerald, M. / Mohan, M. / Crysler, C. / Eisennagel, S. / Dasgupta, M. / McMillan, M. / Spurlino, J.C. / Heubert, N. / Maryanoff, B.E. / Tomczuk, B.E. / Damiano, B.P. / Player, M.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3c27.cif.gz | 70.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3c27.ent.gz | 55.6 KB | Display | PDB format |
PDBx/mmJSON format | 3c27.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c2/3c27 ftp://data.pdbj.org/pub/pdb/validation_reports/c2/3c27 | HTTPS FTP |
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-Related structure data
Related structure data | |
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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/peptide | Mass: 3075.470 Da / Num. of mol.: 1 / Fragment: unp residues 334-359 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin |
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#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Fragment: UNP residues 364-622 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / References: UniProt: P00734, thrombin |
#3: Protein/peptide | Mass: 1411.465 Da / Num. of mol.: 1 / Fragment: unp residues 55-65 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28507, UniProt: P28504*PLUS |
#4: Chemical | ChemComp-DKK / |
#5: 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: 2.67 Å3/Da / Density % sol: 53.97 % |
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-Data collection
Diffraction source | Source: ROTATING ANODE / Type: MACSCIENCE / Wavelength: 1.54 Å |
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Detector | Type: BRUKER SMART 6000 / Detector: CCD / Date: Jun 7, 2002 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.182→50.075 Å / Num. obs: 18406 / Biso Wilson estimate: 24.22 Å2 |
-Processing
Software |
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Refinement | Resolution: 2.182→50.075 Å / FOM work R set: 0.847 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 45.631 Å2 / ksol: 0.354 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 10.18 Å2 / Biso mean: 28.82 Å2 / Biso min: 100.11 Å2
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Refinement step | Cycle: LAST / Resolution: 2.182→50.075 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 7
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