+Open data
-Basic information
Entry | Database: PDB / ID: 6zuh | ||||||
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Title | Crystal Structure of Thrombin in complex with compound17 | ||||||
Components |
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Keywords | BLOOD CLOTTING / COAGULATION / CONVERTION OF FIBRINOGEN TO FIBRIN / BLOOD CLOTTING INHIBITOR / THROMBIN INHIBITOR / HYDROLASE | ||||||
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 / fibrinolysis / regulation of cytosolic calcium ion concentration / 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 / Cell surface interactions at the vascular wall / lipopolysaccharide binding / 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 / platelet activation / response to wounding / 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 / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / blood microparticle / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / 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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.7 Å | ||||||
Authors | Schafer, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Design, Synthesis, and Pharmacological Characterization of a Neutral, Non-Prodrug Thrombin Inhibitor with Good Oral Pharmacokinetics. Authors: Hillisch, A. / Gericke, K.M. / Allerheiligen, S. / Roehrig, S. / Schaefer, M. / Tersteegen, A. / Schulz, S. / Lienau, P. / Gnoth, M. / Puetter, V. / Hillig, R.C. / Heitmeier, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6zuh.cif.gz | 138.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6zuh.ent.gz | 111.5 KB | Display | PDB format |
PDBx/mmJSON format | 6zuh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zu/6zuh ftp://data.pdbj.org/pub/pdb/validation_reports/zu/6zuh | HTTPS FTP |
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-Related structure data
Related structure data | 6tfiC 6zugC 6zunC 6zuuC 6zuwC 6zuxC 6zv7C 6zv8C 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/peptide , 2 types, 2 molecules LI
#1: Protein/peptide | Mass: 4096.534 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin |
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#3: Protein/peptide | Mass: 1420.451 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: Bachem / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28504 |
-Protein / Sugars , 2 types, 2 molecules H
#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin |
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#5: Sugar | ChemComp-NAG / |
-Non-polymers , 3 types, 313 molecules
#4: Chemical | ChemComp-N6H / [ |
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#6: Chemical | ChemComp-DMS / |
#7: Water | ChemComp-HOH / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.52 Å3/Da / Density % sol: 51.16 % |
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Crystal grow | Temperature: 283 K / Method: vapor diffusion, hanging drop Details: 0.02 M phosphate buffer pH 7.5, 27% PEG 8000, 100 mM NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.54187 Å | ||||||||||||||||||||||||||||||
Detector | Type: MAR scanner 300 mm plate / Detector: IMAGE PLATE / Date: Oct 30, 2009 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.54187 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.7→20.43 Å / Num. all: 31839 / Num. obs: 31839 / % possible obs: 82.6 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.047 / Rpim(I) all: 0.029 / Rrim(I) all: 0.056 / Rsym value: 0.047 / Net I/σ(I): 17.9 / Num. measured all: 109295 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: inhouse Resolution: 1.7→15 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.918 / SU B: 3.928 / SU ML: 0.068 / SU R Cruickshank DPI: 0.1226 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.123 / ESU R Free: 0.12 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : WITH TLS ADDED
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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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 71.42 Å2 / Biso mean: 26.847 Å2 / Biso min: 13.22 Å2
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Refinement step | Cycle: final / Resolution: 1.7→15 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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