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- PDB-5qqo: FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(5E,8S)-8-[(6R)-... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5qqo | ||||||
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Title | FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(5E,8S)-8-[(6R)-6-(3-chlorophenyl)-2-oxo-1,3-oxazinan-3-yl]-2-oxo-1,3,4,7,8,10-hexahydro-2H-12,9-(azeno)-1,10-benzodiazacyclotetradecin-15-yl]carbamate | ||||||
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![]() | HYDROLASE / SERINE PROTEASE / BLOOD COAGULATION FACTOR / PROTEIN 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: Structure based design of macrocyclic factor XIa inhibitors: Discovery of cyclic P1 linker moieties with improved oral bioavailability. Authors: Clark, C.G. / Rossi, K.A. / Corte, J.R. / Fang, T. / Smallheer, J.M. / De Lucca, I. / Nirschl, D.S. / Orwat, M.J. / Pinto, D.J.P. / Hu, Z. / Wang, Y. / Yang, W. / Jeon, Y. / Ewing, W.R. / ...Authors: Clark, C.G. / Rossi, K.A. / Corte, J.R. / Fang, T. / Smallheer, J.M. / De Lucca, I. / Nirschl, D.S. / Orwat, M.J. / Pinto, D.J.P. / Hu, Z. / Wang, Y. / Yang, W. / Jeon, Y. / Ewing, W.R. / Myers Jr., J.E. / Sheriff, S. / Lou, Z. / Bozarth, J.M. / Wu, Y. / Rendina, A. / Harper, T. / Zheng, J. / Xin, B. / Xiang, Q. / Luettgen, J.M. / Seiffert, D.A. / Wexler, R.R. / Lam, P.Y.S. #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 2nd., L.M. / Rossi, K.A. / Rendina, A.R. / Bozarth, J.M. / Zhang, G. / Wei, A. / Ramamurthy, V. / ...Authors: Pinto, D.J. / Smallheer, J.M. / Corte, J.R. / Austin, E.J. / Wang, C. / Fang, T. / Smith 2nd., L.M. / Rossi, K.A. / Rendina, A.R. / Bozarth, J.M. / Zhang, G. / Wei, A. / Ramamurthy, V. / Sheriff, S. / Myers Jr., J.E. / Morin, P.E. / Luettgen, J.M. / Seiffert, D.A. / Quan, M.L. / Wexler, R.R. #5: ![]() 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 Jr., 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 Jr., 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. #6: ![]() Title: Novel phenylalanine derived diamides as Factor XIa inhibitors. Authors: Smith 2nd., L.M. / Orwat, M.J. / Hu, Z. / Han, W. / Wang, C. / Rossi, K.A. / Gilligan, P.J. / Pabbisetty, K.B. / Osuna, H. / Corte, J.R. / Rendina, A.R. / Luettgen, J.M. / Wong, P.C. / ...Authors: Smith 2nd., L.M. / Orwat, M.J. / Hu, Z. / Han, W. / Wang, C. / Rossi, K.A. / Gilligan, P.J. / Pabbisetty, K.B. / Osuna, H. / Corte, J.R. / Rendina, A.R. / Luettgen, J.M. / Wong, P.C. / Narayanan, R. / Harper, T.W. / Bozarth, J.M. / Crain, E.J. / Wei, A. / Ramamurthy, V. / Morin, P.E. / Xin, B. / Zheng, J. / Seiffert, D.A. / Quan, M.L. / Lam, P.Y.S. / Wexler, R.R. / Pinto, D.J.P. #7: ![]() Title: Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group. Authors: Corte, J.R. / Fang, T. / Pinto, D.J. / Orwat, M.J. / Rendina, A.R. / Luettgen, J.M. / Rossi, K.A. / Wei, A. / Ramamurthy, V. / Myers Jr., J.E. / Sheriff, S. / Narayanan, R. / Harper, T.W. / ...Authors: Corte, J.R. / Fang, T. / Pinto, D.J. / Orwat, M.J. / Rendina, A.R. / Luettgen, J.M. / Rossi, K.A. / Wei, A. / Ramamurthy, V. / Myers Jr., J.E. / Sheriff, S. / Narayanan, R. / Harper, T.W. / Zheng, J.J. / Li, Y.X. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. #8: ![]() Title: Structure-Based Design of Macrocyclic Factor XIa Inhibitors: Discovery of the Macrocyclic Amide Linker. Authors: Corte, J.R. / Fang, T. / Osuna, H. / Pinto, D.J. / Rossi, K.A. / Myers Jr., J.E. / Sheriff, S. / Lou, Z. / Zheng, J.J. / Harper, T.W. / Bozarth, J.M. / Wu, Y. / Luettgen, J.M. / Seiffert, D. ...Authors: Corte, J.R. / Fang, T. / Osuna, H. / Pinto, D.J. / Rossi, K.A. / Myers Jr., J.E. / Sheriff, S. / Lou, Z. / Zheng, J.J. / Harper, T.W. / Bozarth, J.M. / Wu, Y. / Luettgen, J.M. / Seiffert, D.A. / Decicco, C.P. / Wexler, R.R. / Quan, M.L. #9: ![]() Title: Macrocyclic inhibitors of Factor XIa: Discovery of alkyl-substituted macrocyclic amide linkers with improved potency. Authors: Corte, J.R. / Yang, W. / Fang, T. / Wang, Y. / Osuna, H. / Lai, A. / Ewing, W.R. / Rossi, K.A. / Myers Jr., J.E. / Sheriff, S. / Lou, Z. / Zheng, J.J. / Harper, T.W. / Bozarth, J.M. / Wu, Y. ...Authors: Corte, J.R. / Yang, W. / Fang, T. / Wang, Y. / Osuna, H. / Lai, A. / Ewing, W.R. / Rossi, K.A. / Myers Jr., J.E. / Sheriff, S. / Lou, Z. / Zheng, J.J. / Harper, T.W. / Bozarth, J.M. / Wu, Y. / Luettgen, J.M. / Seiffert, D.A. / Quan, M.L. / Wexler, R.R. / Lam, P.Y.S. #10: ![]() Title: Macrocyclic factor XIa inhibitors. Authors: Wang, C. / Corte, J.R. / Rossi, K.A. / Bozarth, J.M. / Wu, Y. / Sheriff, S. / Myers Jr., J.E. / Luettgen, J.M. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. #11: ![]() Title: Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212). Authors: Pinto, D.J.P. / Orwat, M.J. / Smith 2nd., L.M. / Quan, M.L. / Lam, P.Y.S. / Rossi, K.A. / Apedo, A. / Bozarth, J.M. / Wu, Y. / Zheng, J.J. / Xin, B. / Toussaint, N. / Stetsko, P. / ...Authors: Pinto, D.J.P. / Orwat, M.J. / Smith 2nd., L.M. / Quan, M.L. / Lam, P.Y.S. / Rossi, K.A. / Apedo, A. / Bozarth, J.M. / Wu, Y. / Zheng, J.J. / Xin, B. / Toussaint, N. / Stetsko, P. / Gudmundsson, O. / Maxwell, B. / Crain, E.J. / Wong, P.C. / Lou, Z. / Harper, T.W. / Chacko, S.A. / Myers Jr., J.E. / Sheriff, S. / Zhang, H. / Hou, X. / Mathur, A. / Seiffert, D.A. / Wexler, R.R. / Luettgen, J.M. / Ewing, W.R. #12: ![]() Title: Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors. Authors: Hu, Z. / Wang, C. / Han, W. / Rossi, K.A. / Bozarth, J.M. / Wu, Y. / Sheriff, S. / Myers Jr., J.E. / Luettgen, J.M. / Seiffert, D.A. / Wexler, R.R. / Quan, M.L. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 70.7 KB | Display | ![]() |
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PDB format | ![]() | 55.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 731 KB | Display | ![]() |
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Full document | ![]() | 731.6 KB | Display | |
Data in XML | ![]() | 14 KB | Display | |
Data in CIF | ![]() | 20.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Group deposition
ID | G_1002075 (2 entries) |
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Title | FXIa |
Type | undefined |
Description | Structures deposited in support of C.G. Clark et al., Bioorg.Med.Chem.?, about to be submitted |
-Related structure data
Related structure data | ![]() 4ty7S 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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1 |
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Unit cell |
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Components on special symmetry positions |
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Components
-Protein / Protein/peptide , 2 types, 2 molecules AH
#1: Protein | Mass: 27600.342 Da / Num. of mol.: 1 / Fragment: COAGULATION FACTOR XI, HEAVY CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 2159.419 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Non-polymers , 4 types, 235 molecules ![](data/chem/img/NRJ.gif)
![](data/chem/img/SO4.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/SO4.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/HOH.gif)
#3: Chemical | ChemComp-NRJ / | ||
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#4: Chemical | ChemComp-SO4 / | ||
#5: Chemical | ChemComp-EDO / #6: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.2 Å3/Da / Density % sol: 61.53 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 100 mM sodium acetate, pH 4.6, 25% (w/v) MePEG2000, 200 mM ammonium sulfate, then transferred to 100 mM Tris-HCl, pH 7.0, 25% (w/v) MePEG2000, 200 MM ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() |
Detector | Type: RIGAKU SATURN 92 / Detector: CCD / Date: Dec 10, 2010 / Details: MICROMAX CONFOCAL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 2→106.01 Å / Num. obs: 26197 / % possible obs: 99.2 % / Observed criterion σ(I): 0 / Redundancy: 9.7 % / Biso Wilson estimate: 21.54 Å2 / Rsym value: 0.092 / Net I/σ(I): 21.1 |
Reflection shell | Resolution: 2→2.11 Å / Redundancy: 5.5 % / Mean I/σ(I) obs: 5 / Rsym value: 0.324 / Rejects: 0 / % possible all: 94.7 |
-Phasing
Phasing | Method: ![]() |
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Processing
Software |
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Refinement | Method to determine structure: ![]() Starting model: 4TY7 Resolution: 2→68.3 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.937 / SU R Cruickshank DPI: 0.117 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.125 / SU Rfree Blow DPI: 0.112 / SU Rfree Cruickshank DPI: 0.108
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Displacement parameters | Biso max: 109.61 Å2 / Biso mean: 24.47 Å2 / Biso min: 6.79 Å2
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Refine analyze | Luzzati coordinate error obs: 0.23 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2→68.3 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.08 Å / Total num. of bins used: 13
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