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Yorodumi- PDB-1c5n: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1c5n | |||||||||
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Title | STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR | |||||||||
Components |
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Keywords | HYDROLASE/HYDROLASE INHIBITOR / S1 site inhibitor / urokinase / trypsin / BLOOD CLOTTING / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / 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 / 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 / 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 / serine-type endopeptidase inhibitor activity / antimicrobial humoral immune response mediated by antimicrobial peptide / blood coagulation / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / positive regulation of cell growth / regulation of cell shape / 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 / positive regulation of cell population proliferation / calcium ion binding / 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 / DIFFERENCE FOURIER PLUS REFINEMENT / Resolution: 1.5 Å | |||||||||
Authors | Katz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L. | |||||||||
Citation | Journal: Chem.Biol. / Year: 2000 Title: Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. Authors: Katz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1c5n.cif.gz | 149.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1c5n.ent.gz | 118.6 KB | Display | PDB format |
PDBx/mmJSON format | 1c5n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1c5n_validation.pdf.gz | 817.4 KB | Display | wwPDB validaton report |
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Full document | 1c5n_full_validation.pdf.gz | 825 KB | Display | |
Data in XML | 1c5n_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | 1c5n_validation.cif.gz | 25.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c5/1c5n ftp://data.pdbj.org/pub/pdb/validation_reports/c5/1c5n | HTTPS FTP |
-Related structure data
Related structure data | 1c5lC 1c5mC 1c5oC 1c5pC 1c5qC 1c5rC 1c5sC 1c5tC 1c5uC 1c5vC 1c5wC 1c5xC 1c5yC 1c5zC 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: 1363.399 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Hirudo medicinalis (medicinal leech) / References: UniProt: P28504 |
-Protein , 1 types, 1 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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-Non-polymers , 4 types, 258 molecules
#4: Chemical | ChemComp-NA / |
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#5: Chemical | ChemComp-CA / |
#6: Chemical | ChemComp-ESI / |
#7: 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: 2.65 Å3/Da / Density % sol: 53.61 % | |||||||||||||||||||||||||||||||||||
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Crystal grow | Method: vapor diffusion / pH: 7.5 Details: Thrombin was purchased from Haematologic Technologies, Inc. and acetyl-hirudin from Bachem. Thrombin was prepared as described (Skrzpczak-Jankun et al., 1991). Thrombin (1.0 mg/ml in 50 mM ...Details: Thrombin was purchased from Haematologic Technologies, Inc. and acetyl-hirudin from Bachem. Thrombin was prepared as described (Skrzpczak-Jankun et al., 1991). Thrombin (1.0 mg/ml in 50 mM HEPES, 50 % glycerol, pH 7.0) was incubated with 1.0 mM acetyl-hirudin, 10 mM 4-iodobenzo[b]thiophene-2-carboxamidine for 1 hr at 4 deg C. Glycerol was removed andthe complex concentrated with a centricon 10 (Amicon) to about 10 mg/ml as determined by the Biorad protein assay kit using bovine serum albumin. Crystals of thrombin-acetyl-hirudin-4-iodobenzo[b]thiophene-2-carboxamidine were grown in hanging drops by vapor diffusion after streak seeding. The drops were made from 5 microliters of complex and 5 microliters of reservoir solution (0.10 M Tris,0.50 M NaCl, 22 % (by volume) PEG 4K, pH 7.5)., VAPOR DIFFUSION | |||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS Method: vapor diffusion, hanging drop / Details: used seeding | |||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 298 K |
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Diffraction source | Source: ROTATING ANODE / Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Apr 8, 1999 / Details: MSC MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.5→36.13 Å / Num. all: 43801 / % possible obs: 65 % / Observed criterion σ(I): 1 / Redundancy: 2.1 % / Rmerge(I) obs: 0.063 / Net I/σ(I): 9 |
Reflection shell | Resolution: 1.5→1.57 Å / Rmerge(I) obs: 0.245 / Mean I/σ(I) obs: 1.9 / % possible all: 36.1 |
-Processing
Software |
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Refinement | Method to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT Resolution: 1.5→7.5 Å / Cross valid method: X-PLOR / σ(F): 2 Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Met_H84, Glu_H97A Met_H106, and Met_H210 was simultaneously refined in two conformations. No density was observed ...Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Met_H84, Glu_H97A Met_H106, and Met_H210 was simultaneously refined in two conformations. No density was observed for Trp148, Thr149, Ala149A, Asn149B, Val149C, Gly149D, and Lys149E in the autolysis loop, and these residues are not included in the model. Disordered waters include: HOH395 which is in a special position. HOH396 is close to a symmetry related equivalent of itself; HOH422 which is close to HOH432; HOH434 is close to a symmetry related equivalent of itself; (THE ABOVE WATERS HAVE VERY STRONG DENSITY AND THEIR REFINED OCCUPANCIES ARE SIGNIFICANTLY GREATER THAN UNITY. THEY MAY REFLECT A DIFFERENT FEATURE THAN DISORDERED WATERS); HOH663 which is close to a symmetry-related equivalent of HOH575 and to a symmetry-related equivalent of residue L1E; HOH511 WHICH IS CLOSE TO HOH758; HOH718 WHICH IS CLOSE TO HOH720; HOH586 WHICH IS CLOSE TO HOH721. HIS_H57 IS MONOPROTONATED ON THE DELTA NITROGEN. HIS_H91 and His_H119 are MONOPROTONATED ON the epsilon nitrogen
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Refinement step | Cycle: LAST / Resolution: 1.5→7.5 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.5→1.57 Å / Total num. of bins used: 8
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Xplor file |
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Software | *PLUS Name: X-PLOR / Version: 3.1 / Classification: refinement | |||||||||||||||||||||||||||
Refinement | *PLUS σ(F): 2 / % reflection Rfree: 10 % / Rfactor obs: 0.222 / Rfactor Rwork: 0.22 | |||||||||||||||||||||||||||
Solvent computation | *PLUS | |||||||||||||||||||||||||||
Displacement parameters | *PLUS | |||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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LS refinement shell | *PLUS Rfactor Rfree: 0.508 / Rfactor Rwork: 0.498 |