[English] 日本語
Yorodumi- PDB-4x6p: FACTOR XIA (PICHIA PASTORIS; C500S [C122S]) IN COMPLEX WITH THE I... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4x6p | ||||||
---|---|---|---|---|---|---|---|
Title | FACTOR XIA (PICHIA PASTORIS; C500S [C122S]) IN COMPLEX WITH THE INHIBITOR (2E)-N-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enamide | ||||||
Components | Coagulation factor XI, light chainFactor XI | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / SERINE PROTEASE / BLOOD COAGULATION FACTOR / PROTEIN INHIBITOR COMPLEX / HYDROLASE-HYDROLASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / plasminogen activation / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / heparin binding / serine-type endopeptidase activity / extracellular space ...coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / plasminogen activation / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / heparin binding / serine-type endopeptidase activity / extracellular space / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.93 Å | ||||||
Authors | Sheriff, S. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2015 Title: Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties. Authors: Pinto, D.J. / Smallheer, J.M. / Corte, J.R. / Austin, E.J. / Wang, C. / Fang, T. / Smith, L.M. / Rossi, K.A. / Rendina, A.R. / Bozarth, J.M. / Zhang, G. / Wei, A. / Ramamurthy, V. / Sheriff, ...Authors: Pinto, D.J. / Smallheer, J.M. / Corte, J.R. / Austin, E.J. / Wang, C. / Fang, T. / Smith, L.M. / Rossi, K.A. / Rendina, A.R. / Bozarth, J.M. / Zhang, G. / Wei, A. / Ramamurthy, V. / Sheriff, S. / Myers, J.E. / Morin, P.E. / Luettgen, J.M. / Seiffert, D.A. / Quan, M.L. / Wexler, R.R. #1: Journal: J.Med.Chem. / Year: 2014 Title: Tetrahydroquinoline derivatives as potent and selective factor XIa inhibitors. Authors: Quan, M.L. / Wong, P.C. / Wang, C. / Woerner, F. / Smallheer, J.M. / Barbera, F.A. / Bozarth, J.M. / Brown, R.L. / Harpel, M.R. / Luettgen, J.M. / Morin, P.E. / Peterson, T. / Ramamurthy, V. ...Authors: Quan, M.L. / Wong, P.C. / Wang, C. / Woerner, F. / Smallheer, J.M. / Barbera, F.A. / Bozarth, J.M. / Brown, R.L. / Harpel, M.R. / Luettgen, J.M. / Morin, P.E. / Peterson, T. / Ramamurthy, V. / Rendina, A.R. / Rossi, K.A. / Watson, C.A. / Wei, A. / Zhang, G. / Seiffert, D. / Wexler, R.R. #2: Journal: J.Med.Chem. / Year: 2014 Title: Phenylimidazoles as potent and selective inhibitors of coagulation factor XIa with in vivo antithrombotic activity. Authors: Hangeland, J.J. / Friends, T.J. / Rossi, K.A. / Smallheer, J.M. / Wang, C. / Sun, Z. / Corte, J.R. / Fang, T. / Wong, P.C. / Rendina, A.R. / Barbera, F.A. / Bozarth, J.M. / Luettgen, J.M. / ...Authors: Hangeland, J.J. / Friends, T.J. / Rossi, K.A. / Smallheer, J.M. / Wang, C. / Sun, Z. / Corte, J.R. / Fang, T. / Wong, P.C. / Rendina, A.R. / Barbera, F.A. / Bozarth, J.M. / Luettgen, J.M. / Watson, C.A. / Zhang, G. / Wei, A. / Ramamurthy, V. / Morin, P.E. / Bisacchi, G.S. / Subramaniam, S. / Arunachalam, P. / Mathur, A. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. #3: Journal: Bioorg.Med.Chem.Lett. / Year: 2015 Title: Pyridine and pyridinone-based factor XIa inhibitors. Authors: Corte, J.R. / Fang, T. / Hangeland, J.J. / Friends, T.J. / Rendina, A.R. / Luettgen, J.M. / Bozarth, J.M. / Barbera, F.A. / Rossi, K.A. / Wei, A. / Ramamurthy, V. / Morin, P.E. / Seiffert, D. ...Authors: Corte, J.R. / Fang, T. / Hangeland, J.J. / Friends, T.J. / Rendina, A.R. / Luettgen, J.M. / Bozarth, J.M. / Barbera, F.A. / Rossi, K.A. / Wei, A. / Ramamurthy, V. / Morin, P.E. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4x6p.cif.gz | 119.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4x6p.ent.gz | 92.5 KB | Display | PDB format |
PDBx/mmJSON format | 4x6p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x6/4x6p ftp://data.pdbj.org/pub/pdb/validation_reports/x6/4x6p | HTTPS FTP |
---|
-Related structure data
Related structure data | 4x6mC 4x6nC 4x6oC 3sorS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
| ||||||||
Details | chain A |
-Components
-Protein / Sugars , 2 types, 4 molecules AB
#1: Protein | Mass: 26856.496 Da / Num. of mol.: 2 / Mutation: C500S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: F11 / Plasmid: pPICZalphaA / Production host: Komagataella pastoris (fungus) / Strain (production host): SMD1168H / References: UniProt: P03951, coagulation factor XIa #2: Sugar | |
---|
-Non-polymers , 4 types, 315 molecules
#3: Chemical | #4: Chemical | ChemComp-CIT / | #5: Chemical | ChemComp-GOL / #6: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.31 Å3/Da / Density % sol: 46.8 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 5 / Details: 100 MM SODIUM CITRATE, PH 5.0, 36%(w/v) PEG4000 |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 27, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.93→41.27 Å / Num. obs: 38006 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 6.6 % / Biso Wilson estimate: 23.45 Å2 / Rmerge(I) obs: 0.093 / Net I/σ(I): 14.5 |
Reflection shell | Resolution: 1.93→2.03 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.517 / Mean I/σ(I) obs: 3.3 / % possible all: 99.9 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3SOR Resolution: 1.93→27.47 Å / Cor.coef. Fo:Fc: 0.9528 / Cor.coef. Fo:Fc free: 0.9339 / SU R Cruickshank DPI: 0.142 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.147 / SU Rfree Blow DPI: 0.128 / SU Rfree Cruickshank DPI: 0.126
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24.3 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.171 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.93→27.47 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.93→1.98 Å / Total num. of bins used: 19
|