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Yorodumi- PDB-2vip: Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioa... -
+Open data
-Basic information
Entry | Database: PDB / ID: 2vip | ||||||
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Title | Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator | ||||||
Components | UROKINASE-TYPE PLASMINOGEN ACTIVATOR CHAIN B | ||||||
Keywords | HYDROLASE / PLASMINOGEN ACTIVATION / EGF-LIKE DOMAIN / BLOOD COAGULATION / INHIBITOR / POLYMORPHISM / GLYCOPROTEIN / FIBRINOLYSIS / KRINGLE / ZYMOGEN / SECRETED / PROTEASE / UROKINASE-TYPE PLASMINOGEN ACTIVATOR / PHARMACEUTICAL / SERINE PROTEASE / PHOSPHORYLATION | ||||||
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 / serine protease inhibitor complex / plasminogen activation / regulation of cell adhesion mediated by integrin / tertiary granule membrane / negative regulation of fibrinolysis / regulation of cell adhesion / specific granule membrane / 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 / OTHER / Resolution: 1.72 Å | ||||||
Authors | Frederickson, M. / Callaghan, O. / Chessari, G. / Congreve, M. / Cowan, S.R. / Matthews, J.E. / McMenamin, R. / Smith, D. / Vinkovic, M. / Wallis, N.G. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator Authors: Frederickson, M. / Callaghan, O. / Chessari, G. / Congreve, M. / Cowan, S.R. / Matthews, J.E. / Mcmenamin, R. / Smith, D. / Vinkovic, M. / Wallis, N.G. | ||||||
History |
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Remark 700 | SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 8-STRANDED BARREL THIS IS REPRESENTED BY A 9-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. THE SHEETS PRESENTED AS "AB" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 7-STRANDED BARREL THIS IS REPRESENTED BY A 8-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2vip.cif.gz | 70.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2vip.ent.gz | 56.8 KB | Display | PDB format |
PDBx/mmJSON format | 2vip.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vi/2vip ftp://data.pdbj.org/pub/pdb/validation_reports/vi/2vip | 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 | Mass: 28444.346 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, RESIDUES 179-431 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P00749, u-plasminogen activator |
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#2: Chemical | ChemComp-ACT / |
#3: Chemical | ChemComp-SO4 / |
#4: Chemical | ChemComp-L1R / |
#5: Water | ChemComp-HOH / |
Compound details | ENGINEERED |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.71 Å3/Da / Density % sol: 27.7 % / Description: NONE |
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Crystal grow | pH: 6.6 Details: PROTEIN WAS CRYSTALLIZED FROM 22-24% PEG4000, 0.17M (NH4)2SO4, 15% GLYCEROL, 0.1M NA(CH3COO) PH=4.0; THEN SOAKED IN 0.01M COMPOUND, 28% PEG4000, 0.29M HEPES PH=6.6, 5% GLYCEROL, 0.001M ...Details: PROTEIN WAS CRYSTALLIZED FROM 22-24% PEG4000, 0.17M (NH4)2SO4, 15% GLYCEROL, 0.1M NA(CH3COO) PH=4.0; THEN SOAKED IN 0.01M COMPOUND, 28% PEG4000, 0.29M HEPES PH=6.6, 5% GLYCEROL, 0.001M NA(CH3COO), 0.001M (NH4)2SO4, 10% DMSO |
-Data collection
Diffraction | Mean temperature: 93 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 |
Detector | Type: RIGAKU CCD / Detector: CCD / Details: OSMIC BLUE CONFOCAL OPTICS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.72→27.63 Å / Num. obs: 20118 / % possible obs: 79.6 % / Observed criterion σ(I): 0 / Redundancy: 2.5 % / Rmerge(I) obs: 0.06 |
Reflection shell | Resolution: 1.72→1.78 Å / Rmerge(I) obs: 0.3 / Mean I/σ(I) obs: 2.1 / % possible all: 18 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER Starting model: NONE Resolution: 1.72→27.62 Å / Cross valid method: THROUGHOUT / σ(F): 0
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Refinement step | Cycle: LAST / Resolution: 1.72→27.62 Å
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