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Yorodumi- PDB-5tnt: Discovery of novel aminobenzisoxazole derivatives as orally avail... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5tnt | ||||||
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Title | Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors | ||||||
Components | (Coagulation factor ...) x 2 | ||||||
Keywords | HYDROLASE/HYDROLASE inhibitor / SERINE PROTEINASE / BLOOD COAGULATION / COAGULATION FACTOR / HYDROLASE-2 / HYDROLASE INHIBITOR COMPLEX / HYDROLASE-HYDROLASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information Defective F9 secretion / Defective gamma-carboxylation of F9 / coagulation factor IXa / Defective F9 activation / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / zymogen activation / Extrinsic Pathway of Fibrin Clot Formation / Protein hydroxylation ...Defective F9 secretion / Defective gamma-carboxylation of F9 / coagulation factor IXa / Defective F9 activation / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / zymogen activation / Extrinsic Pathway of Fibrin Clot Formation / Protein hydroxylation / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Removal of aminoterminal propeptides from gamma-carboxylated proteins / Intrinsic Pathway of Fibrin Clot Formation / Golgi lumen / blood coagulation / collagen-containing extracellular matrix / endopeptidase activity / endoplasmic reticulum lumen / serine-type endopeptidase activity / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å | ||||||
Authors | Sakurada, I. / Endo, T. / Hikita, K. / Hirabayashi, T. / Hosaka, Y. / Kato, Y. / Maeda, Y. / Matsumoto, S. / Mizuno, T. / Nagasue, A. ...Sakurada, I. / Endo, T. / Hikita, K. / Hirabayashi, T. / Hosaka, Y. / Kato, Y. / Maeda, Y. / Matsumoto, S. / Mizuno, T. / Nagasue, A. / Nishimura, T. / Shimada, S. / Shinozaki, M. / Taguchi, K. / Takeuchi, K. / Yokoyama, T. / Hruza, A. / Reichert, P. / Zhang, T. / Wood, H.B. / Nakao, K. / Furusako, S. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2017 Title: Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors. Authors: Sakurada, I. / Endo, T. / Hikita, K. / Hirabayashi, T. / Hosaka, Y. / Kato, Y. / Maeda, Y. / Matsumoto, S. / Mizuno, T. / Nagasue, H. / Nishimura, T. / Shimada, S. / Shinozaki, M. / Taguchi, ...Authors: Sakurada, I. / Endo, T. / Hikita, K. / Hirabayashi, T. / Hosaka, Y. / Kato, Y. / Maeda, Y. / Matsumoto, S. / Mizuno, T. / Nagasue, H. / Nishimura, T. / Shimada, S. / Shinozaki, M. / Taguchi, K. / Takeuchi, K. / Yokoyama, T. / Hruza, A. / Reichert, P. / Zhang, T. / Wood, H.B. / Nakao, K. / Furusako, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5tnt.cif.gz | 257.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5tnt.ent.gz | 206.3 KB | Display | PDB format |
PDBx/mmJSON format | 5tnt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5tnt_validation.pdf.gz | 744.3 KB | Display | wwPDB validaton report |
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Full document | 5tnt_full_validation.pdf.gz | 745.9 KB | Display | |
Data in XML | 5tnt_validation.xml.gz | 16.7 KB | Display | |
Data in CIF | 5tnt_validation.cif.gz | 25.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tn/5tnt ftp://data.pdbj.org/pub/pdb/validation_reports/tn/5tnt | HTTPS FTP |
-Related structure data
Related structure data | 5tnoC 1rfnS C: citing same article (ref.) S: Starting model for refinement |
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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
-Coagulation factor ... , 2 types, 2 molecules AB
#1: Protein | Mass: 26104.703 Da / Num. of mol.: 1 / Fragment: UNP residues 227-461 / Mutation: R150A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: F9 / Production host: Escherichia coli (E. coli) / References: UniProt: P00740, coagulation factor IXa |
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#2: Protein | Mass: 6841.809 Da / Num. of mol.: 1 / Fragment: UNP residues 131-191 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: F9 / Production host: Escherichia coli (E. coli) / References: UniProt: P00740, coagulation factor IXa |
-Non-polymers , 4 types, 347 molecules
#3: Chemical | ChemComp-7GQ / |
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#4: Chemical | ChemComp-NA / |
#5: Chemical | ChemComp-NHE / |
#6: 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: 2.78 Å3/Da / Density % sol: 55.82 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 9 Details: 50 MM CHES, PH 9.0, 1.3 M TRI-SODIUM CITRATE AND 3 MM COMPOUND (CROSS SEEDED WITH CRYSTALS GROWN FROM REMARK 280 50 MM TRIS, PH 7.2, 1.45 M AMMONIUM SULFATE, 2.0 M SODIUM CHLORIDE AND 3 MM COMPOUND) |
-Data collection
Diffraction | Mean temperature: 95 K |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.97949 Å |
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: May 26, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→28.6 Å / Num. obs: 68182 / % possible obs: 99.8 % / Redundancy: 5.6 % / Biso Wilson estimate: 17.95 Å2 / Rmerge(I) obs: 0.092 / Rsym value: 0.092 / Net I/σ(I): 11.7 |
Reflection shell | Resolution: 1.4→1.404 Å / Redundancy: 5.6 % / Rmerge(I) obs: 0.446 / Mean I/σ(I) obs: 3.4 / Rsym value: 0.446 / % possible all: 91.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1RFN Resolution: 1.4→20.5 Å / Cor.coef. Fo:Fc: 0.972 / Cor.coef. Fo:Fc free: 0.969 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.048 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.046 / SU Rfree Blow DPI: 0.046 / SU Rfree Cruickshank DPI: 0.045
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Displacement parameters | Biso mean: 25.14 Å2
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Refine analyze | Luzzati coordinate error obs: 0.14 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.4→20.5 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.4→1.44 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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