+Open data
-Basic information
Entry | Database: PDB / ID: 1qhr | ||||||
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Title | NOVEL COVALENT ACTIVE SITE THROMBIN INHIBITORS | ||||||
Components |
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Keywords | BLOOD CLOTTING/HYDROLASE INHIBITOR / PROTEINASE / BLOOD COAGULATION / TRYPSIN LIKE PROTEINASE / COMPLEX (SERINE PROTEASE-INHIBITOR) / BLOOD CLOTTING-HYDROLASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information negative regulation of serine-type peptidase activity / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway ...negative regulation of serine-type peptidase activity / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / negative regulation of platelet activation / 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 / acute-phase response / Regulation of Complement cascade / negative regulation of proteolysis / Cell surface interactions at the vascular wall / lipopolysaccharide binding / 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 / positive regulation of protein localization to nucleus / Golgi lumen / 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / blood coagulation / 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 / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / 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 / OTHER / Resolution: 2.2 Å | ||||||
Authors | Jhoti, H. / Cleasby, A. / Reid, S. / Thomas, P. / Wonacott, A. | ||||||
Citation | Journal: Biochemistry / Year: 1999 Title: Crystal structures of thrombin complexed to a novel series of synthetic inhibitors containing a 5,5-trans-lactone template. Authors: Jhoti, H. / Cleasby, A. / Reid, S. / Thomas, P.J. / Weir, M. / Wonacott, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1qhr.cif.gz | 81.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1qhr.ent.gz | 60 KB | Display | PDB format |
PDBx/mmJSON format | 1qhr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qh/1qhr ftp://data.pdbj.org/pub/pdb/validation_reports/qh/1qhr | 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/peptide | Mass: 4096.534 Da / Num. of mol.: 1 / Fragment: LIGHT CHAIN / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: BLOOD PLASMA / References: UniProt: P00734, thrombin |
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#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Fragment: HEAVY CHAIN / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: BLOOD PLASMA / References: UniProt: P00734, thrombin |
#3: Protein/peptide | Mass: 1363.399 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: THIS PEPTIDE WAS CHEMICALLY SYNTHESIZED. THE SEQUENCE FOR THIS PEPTIDE OCCURS NATURALLY IN MEDICINAL LEECH (HIRUDO MEDICINALIS). Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28501, UniProt: P01050*PLUS |
#4: Chemical | ChemComp-157 / |
#5: Water | ChemComp-HOH / |
Nonpolymer details | GR15: ACTIVE SITE DIRECTED, ACYLATING INHIBITOR OF THROMBIN. |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.62 Å3/Da / Density % sol: 53.11 % | ||||||||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | pH: 7 Details: CRYSTALS WERE GROWN BY MACROSEEDING A SOLUTION OF 100MM HEPES PH 7.0, 22% PEG4K, 200MM NACL. PROTEIN CONCENTRATION OF 5MG/ML. | ||||||||||||||||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS pH: 7.3 / Method: vapor diffusion, hanging drop / Details: Skrzypczak, J., (1991) J. Mol. Biol., 221, 1379. | ||||||||||||||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 290 K |
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Diffraction source | Source: ROTATING ANODE / Type: ENRAF-NONIUS / Wavelength: 1.5418 |
Detector | Type: ENRAF-NONIUS / Detector: AREA DETECTOR / Details: MONOCHROMATOR |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2→30 Å / Num. obs: 21972 / % possible obs: 98 % / Redundancy: 2.2 % / Rsym value: 0.06 |
Reflection | *PLUS Rmerge(I) obs: 0.058 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER / Resolution: 2.2→15 Å / σ(F): 2 /
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Refinement step | Cycle: LAST / Resolution: 2.2→15 Å
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Refine LS restraints |
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Software | *PLUS Name: X-PLOR / Version: 3.1 / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | *PLUS Highest resolution: 2.2 Å / Lowest resolution: 15 Å / σ(F): 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints | *PLUS Type: x_angle_deg / Dev ideal: 3.1 |