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Yorodumi- PDB-5egm: Development of a novel tricyclic class of potent and selective FI... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5egm | ||||||
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Title | Development of a novel tricyclic class of potent and selective FIXa inhibitors | ||||||
Components | (Coagulation factor ...Coagulation) 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 / MOLECULAR REPLACEMENT / Resolution: 1.841 Å | ||||||
Authors | Meng, D. / Andre, P. / Bateman, T.J. / Berger, R. / Chen, Y. / Desai, K. / Dewnani, S. / Ellsworth, K. / Feng, D. / Geissler, W.M. ...Meng, D. / Andre, P. / Bateman, T.J. / Berger, R. / Chen, Y. / Desai, K. / Dewnani, S. / Ellsworth, K. / Feng, D. / Geissler, W.M. / Guo, L. / Hruza, A. / Jian, T. / Li, H. / Parker, D.L. / Reichert, P. / Sherer, E.C. / Smith, C.J. / Sonatore, L.M. / Tschirret-Guth, R. / Wu, J. / Xu, J. / Zhang, T. / Campeau, L. / Orr, R. / Poirier, M. / McCabe-Dunn, j. / Araki, K. / Nishimura, T. / Sakurada, I. / Hirabayashi, T. / Wood, H.B. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2015 Title: Development of a novel tricyclic class of potent and selective FIXa inhibitors. Authors: Meng, D. / Andre, P. / Bateman, T.J. / Berger, R. / Chen, Y.H. / Desai, K. / Dewnani, S. / Ellsworth, K. / Feng, D. / Geissler, W.M. / Guo, L. / Hruza, A. / Jian, T. / Li, H. / Metzger, J. / ...Authors: Meng, D. / Andre, P. / Bateman, T.J. / Berger, R. / Chen, Y.H. / Desai, K. / Dewnani, S. / Ellsworth, K. / Feng, D. / Geissler, W.M. / Guo, L. / Hruza, A. / Jian, T. / Li, H. / Metzger, J. / Parker, D.L. / Reichert, P. / Sherer, E.C. / Smith, C.J. / Sonatore, L.M. / Tschirret-Guth, R. / Wu, J. / Xu, J. / Zhang, T. / Campeau, L.C. / Orr, R. / Poirier, M. / McCabe-Dunn, J. / Araki, K. / Nishimura, T. / Sakurada, I. / Hirabayashi, T. / Wood, H.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5egm.cif.gz | 252.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5egm.ent.gz | 201 KB | Display | PDB format |
PDBx/mmJSON format | 5egm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eg/5egm ftp://data.pdbj.org/pub/pdb/validation_reports/eg/5egm | HTTPS FTP |
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-Related structure data
Related structure data | 1rfnS 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 / Mutation: A150R 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, 224 molecules
#3: Chemical | ChemComp-NA / |
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#4: Chemical | ChemComp-NHE / |
#5: Chemical | ChemComp-5NY / |
#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: 2.81 Å3/Da / Density % sol: 56.17 % |
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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 REMARK 280 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 REMARK ...Details: 50 MM CHES, PH 9.0, 1.3 M TRI-SODIUM REMARK 280 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 REMARK 280 CHLORIDE AND 3 MM COMPOUND) |
-Data collection
Diffraction | Mean temperature: 95 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54178 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jan 30, 2013 |
Radiation | Monochromator: Osmic / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 1.841→41.47 Å / Num. all: 105568 / Num. obs: 29836 / % possible obs: 98.9 % / Redundancy: 3.5 % / Biso Wilson estimate: 26.75 Å2 / Rmerge(I) obs: 0.052 / Rsym value: 0.052 / Net I/σ(I): 16 |
Reflection shell | Resolution: 1.841→1.848 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.495 / Mean I/σ(I) obs: 2.7 / % possible all: 98.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1RFN Resolution: 1.841→23.25 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.959 / SU R Cruickshank DPI: 0.135 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.097 / SU Rfree Blow DPI: 0.091 / SU Rfree Cruickshank DPI: 0.093
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Displacement parameters | Biso mean: 34.6 Å2
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Refine analyze | Luzzati coordinate error obs: 0.185 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.841→23.25 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.84→1.91 Å / Total num. of bins used: 15
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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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