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- PDB-4y8x: Factor XIa in complex with the inhibitor methyl (4-{4-chloro-2-[(... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4y8x | ||||||
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Title | Factor XIa in complex with the inhibitor methyl (4-{4-chloro-2-[(1S)-1-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-2-phenylethyl]-1H-imidazol-5-yl}phenyl)carbamate | ||||||
![]() | Coagulation factor XIa | ||||||
![]() | HYDROLASE/HYDROLASE INHIBITOR / hydrolase / serine protease / blood coagulation factor / protein inhibitor complex / HYDROLASE-HYDROLASE INHIBITOR complex | ||||||
Function / homology | ![]() 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Sheriff, S. | ||||||
![]() | ![]() Title: Discovery of a Potent Parenterally Administered Factor XIa Inhibitor with Hydroxyquinolin-2(1H)-one as the P2' Moiety. Authors: Hu, Z. / Wong, P.C. / Gilligan, P.J. / Han, W. / Pabbisetty, K.B. / Bozarth, J.M. / Crain, E.J. / Harper, T. / Luettgen, J.M. / Myers, J.E. / Ramamurthy, V. / Rossi, K.A. / Sheriff, S. / ...Authors: Hu, Z. / Wong, P.C. / Gilligan, P.J. / Han, W. / Pabbisetty, K.B. / Bozarth, J.M. / Crain, E.J. / Harper, T. / Luettgen, J.M. / Myers, J.E. / Ramamurthy, V. / Rossi, K.A. / Sheriff, S. / Watson, C.A. / Wei, A. / Zheng, J.J. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. #1: ![]() 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: ![]() 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: ![]() 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. #4: ![]() 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 72.7 KB | Display | ![]() |
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PDB format | ![]() | 52.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 751.4 KB | Display | ![]() |
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Full document | ![]() | 751.1 KB | Display | |
Data in XML | ![]() | 13.5 KB | Display | |
Data in CIF | ![]() | 19.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4y8yC ![]() 4y8zC ![]() 4ty7S C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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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 | Mass: 27600.342 Da / Num. of mol.: 1 / Fragment: light chain (UNP residues 388-625) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||
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#2: Chemical | ChemComp-4GR / | ||||
#3: Chemical | #4: Chemical | ChemComp-EDO / #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.59 Å3/Da / Density % sol: 65.73 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 100 mM sodium acetate, pH 4.6, 26% w/v MEPEG2000, 200 mM ammonium sulfate (crystals were grown at pH4.6 and transferred to pH 7 prior to soaking with compound) |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 18, 2010 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→106.32 Å / Num. obs: 30451 / % possible obs: 100 % / Observed criterion σ(I): 0 / Redundancy: 12.3 % / Biso Wilson estimate: 23.83 Å2 / Rmerge(I) obs: 0.072 / Net I/σ(I): 27.5 |
Reflection shell | Resolution: 1.9→2.01 Å / Redundancy: 12.7 % / Rmerge(I) obs: 0.399 / Mean I/σ(I) obs: 8.3 / Rejects: 0 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB entry 4TY7 Resolution: 1.9→57.42 Å / Cor.coef. Fo:Fc: 0.9498 / Cor.coef. Fo:Fc free: 0.9497 / SU R Cruickshank DPI: 0.095 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.1 / SU Rfree Blow DPI: 0.086 / SU Rfree Cruickshank DPI: 0.083
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Displacement parameters | Biso max: 96.49 Å2 / Biso mean: 27.12 Å2 / Biso min: 11.22 Å2
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Refine analyze | Luzzati coordinate error obs: 0.157 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.9→57.42 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.9→1.97 Å / Total num. of bins used: 15
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