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Yorodumi- PDB-1c5z: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1c5z | |||||||||
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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 / tertiary granule membrane / regulation of cell adhesion mediated by integrin / negative regulation of fibrinolysis / specific granule membrane / regulation of cell adhesion / 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: 1.85 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 | 1c5z.cif.gz | 138.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1c5z.ent.gz | 111 KB | Display | PDB format |
PDBx/mmJSON format | 1c5z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c5/1c5z ftp://data.pdbj.org/pub/pdb/validation_reports/c5/1c5z | 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 1c5yC C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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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-BEN / | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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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 benzamidne for 15 min on ice. The complex was crystallized by vapor diffusion in ...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 benzamidne 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 | Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: May 12, 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: 1.48→38.25 Å / Num. all: 16139 / % possible obs: 64 % / Observed criterion σ(I): 1 / Redundancy: 1.8 % / Rmerge(I) obs: 0.093 / Net I/σ(I): 4.5 |
Reflection shell | Resolution: 1.85→1.93 Å / Rmerge(I) obs: 0.21 / Mean I/σ(I) obs: 2 / % possible all: 31 |
-Processing
Software |
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Refinement | Method to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT Starting model: PDB1LMW Resolution: 1.85→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 invluded 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 invluded for the A-chain. Residues prior and after these residues are not visible (disordered). Residues after Thr_B242 are not visible (disordered). Residues simultaneously refined in two or more conformations are: Ile_B17, Met_B47, Met_B81, Glu_B86, GLu_B10B, Leu_B123, Thr_B139, Arg_B166, Ser_B232, Leu_B235 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: HOH4 WHICH IS CLOSE TO HOH28; HOH26 WHICH IS CLOSE TO HOH68; HOH47 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF; HOH138 WHICH IS CLOSE TO HOH144; HOH156 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH157; HOH148 WHICH IS CLOSE TO CONFORMATION 1 OF ARG_B166; HOH199 WHICH IS CLOSE TO HOH202; HOH283 WHICH IS CLOSE TO HOH285; HOH290 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH309; HOH291 WHICH IS CLOSE TO HOH298; HOH306 WHICH IS CLOSE TO HOH914; HOH369 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH804; HOH432 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH433; HOH153 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH894; HOH82 WHICH IS CLOSE TO A SYMMETRY- EQUIVALENT OF HOH147; HOH319 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF HOH376; HOH373 WHICH IS CLOSE TO HOH374; HOH400 WHICH IS CLOSE TO HOH412; HOH450 WHICH IS CLOSE TO HOH846; HOH456 WHICH IS CLOSE TO HOH847; HOH715 WHICH IS CLOSE TO HOH720; HOH580 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF; HOH832 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF LYS_B187; HOH917 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF; HOH920 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF; HOH930 WHICH IS CLOSE TO A SYMMETRY-RELATED EQUIVALENT OF ITSELF.
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Refinement step | Cycle: LAST / Resolution: 1.85→7.5 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.85→1.93 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: 0.189 | |||||||||||||||||||||||||||
Solvent computation | *PLUS | |||||||||||||||||||||||||||
Displacement parameters | *PLUS | |||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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LS refinement shell | *PLUS Rfactor Rfree: 0.33 / % reflection Rfree: 10 % / Rfactor Rwork: 0.316 |