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Yorodumi- PDB-1c5y: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1c5y | ||||||
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Title | STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR | ||||||
Components | (PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)) x 2 | ||||||
Keywords | BLOOD CLOTTING / selective / S1 site inhibitor / structure-based drug design / urokinase / trypsin / thrombin | ||||||
Function / homology | Function and homology information u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / regulation of signaling receptor activity ...u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / regulation of signaling receptor activity / serine-type endopeptidase complex / Dissolution of Fibrin Clot / smooth muscle cell migration / plasminogen activation / regulation of cell adhesion mediated by integrin / tertiary granule membrane / negative regulation of fibrinolysis / regulation of cell adhesion / specific granule membrane / serine protease inhibitor complex / fibrinolysis / chemotaxis / blood coagulation / regulation of cell population proliferation / response to hypoxia / positive regulation of cell migration / external side of plasma membrane / serine-type endopeptidase activity / focal adhesion / Neutrophil degranulation / cell surface / signal transduction / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / DIFFERENCE FOURIER PLUS REFINEMENT / Resolution: 1.65 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 | 1c5y.cif.gz | 138.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1c5y.ent.gz | 111 KB | Display | PDB format |
PDBx/mmJSON format | 1c5y.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c5/1c5y ftp://data.pdbj.org/pub/pdb/validation_reports/c5/1c5y | HTTPS FTP |
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-Related structure data
Related structure data | 1c5lC 1c5mC 1c5nC 1c5oC 1c5pC 1c5qC 1c5rC 1c5sC 1c5tC 1c5uC 1c5vC 1c5wC 1c5xC 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 on special symmetry positions |
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-Components
#1: Protein/peptide | Mass: 2708.183 Da / Num. of mol.: 1 / Fragment: SHORT CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: PPIC9 / Production host: Pichia pastoris (fungus) / Strain (production host): HISTIDINE DEFICIENT GS115 / References: UniProt: P00749, u-plasminogen activator | ||||
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#2: Protein | Mass: 28435.428 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: PPIC9 / Production host: Pichia pastoris (fungus) / Strain (production host): HISTIDINE DEFICIENT GS115 / References: UniProt: P00749, u-plasminogen activator | ||||
#3: Chemical | #4: Chemical | ChemComp-ESP / | #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: 1.99 Å3/Da / Density % sol: 25.6 % | ||||||||||||||||||||||||||||||
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Crystal grow | pH: 6.5 Details: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.0, 5.0 mM thieno[2,3-b]pyridine-2-carboxamidine for 15 min on ice. The complex was ...Details: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.0, 5.0 mM thieno[2,3-b]pyridine-2-carboxamidine for 15 min on ice. The complex was crystallized by vapor diffusion in hanging drops containing equal volumes of protein-inhibitor solution (0.28 mM uPA/A145, 1.4 mM inhibitor and well solution (20 % 2-propanol, 20 % PEG 4K, 100 mM sodium citrate, pH 6.5) sealed over the well. | ||||||||||||||||||||||||||||||
Crystal grow | *PLUS pH: 7.4 / Method: vapor diffusion, hanging drop | ||||||||||||||||||||||||||||||
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: Jul 28, 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: 1.44→31.26 Å / Num. all: 23222 / % possible obs: 68 % / Observed criterion σ(I): 0.8 / Redundancy: 1.8 % / Rmerge(I) obs: 0.087 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 1.65→1.72 Å / Rmerge(I) obs: 0.255 / Mean I/σ(I) obs: 1.5 / % possible all: 32.1 |
-Processing
Software |
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Refinement | Method to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT Starting model: PDB1LMW Resolution: 1.65→7.5 Å / Cross valid method: X-PLOR / σ(F): 1.9 Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible ...Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible (disordered). Residues after Glu_B245 are not visible (disordered). Density for Lys_B243 through Glu_B245 is weak or absent Residues simultaneously refined in two or more conformations are: Ile_B17, Met_B47, Met_B81, Glu_B84, Glu_B86, Leu_B123, Thr_B139, Arg_B166, Gln_B192, Ser_B232, Leu_B235, the inhibitor (246). No energy terms between citrate 1 and 2 are included because they appear to be hydrogen-bonded to one another via an unusually short hydrogen bond between carboxylate groups. Disordered waters are: HOH75 which is close to HOH76; HOH247 which is close to a symmetry-related equivalent of HOH248 which in turn is close to HOH249; HOH104 which is close to HOH105; HOH155 which is close to conformation 1 of Glu_B84; HOH292 which is close to HOH298; HOH373 which is close to HOH374; HOH715 which is close to HOH720 which in turn is close to HOH721; HOH598 WHICH IS CLOSE TO HOH831; HOH70 WHICH IS CLOSE TO HOH364; HOH401 WHICH IS CLOSE TO HOH846; HOH462 WHICH IS CLOSE TO HOH465; HOH451 WHICH IS CLOSE TO HOH719; HOH423 WHICH IS CLOSE TO HOH429; HOH358 WHICH IS CLOSE TO HOH910; HOH30 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF; HOH25 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH318; HOH38 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH694; HOH146 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH375; HOH17 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH82.
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Refinement step | Cycle: LAST / Resolution: 1.65→7.5 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.65→1.72 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 Lowest resolution: 7.5 Å / σ(F): 1.9 / % reflection Rfree: 10 % / Rfactor obs: 0.203 / Rfactor Rwork: 0.2 | |||||||||||||||||||||||||||
Solvent computation | *PLUS | |||||||||||||||||||||||||||
Displacement parameters | *PLUS | |||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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LS refinement shell | *PLUS Rfactor Rfree: 0.449 / % reflection Rfree: 10 % / Rfactor Rwork: 0.41 |