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Yorodumi- PDB-2p3t: Crystal structure of human factor XA complexed with 3-Chloro-4-(2... -
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-Basic information
Entry | Database: PDB / ID: 2p3t | ||||||
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Title | Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide | ||||||
Components | (Coagulation factor ...) x 2 | ||||||
Keywords | BLOOD CLOTTING / protein inhibitor complex / nonamidine / coagulation cofactor / protease | ||||||
Function / homology | Function and homology information coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins ...coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / Intrinsic Pathway of Fibrin Clot Formation / phospholipid binding / Golgi lumen / blood coagulation / positive regulation of cell migration / endoplasmic reticulum lumen / external side of plasma membrane / serine-type endopeptidase activity / calcium ion binding / proteolysis / extracellular space / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.92 Å | ||||||
Authors | Adler, M. / Whitlow, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2007 Title: Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors. Authors: Ye, B. / Arnaiz, D.O. / Chou, Y.L. / Griedel, B.D. / Karanjawala, R. / Lee, W. / Morrissey, M.M. / Sacchi, K.L. / Sakata, S.T. / Shaw, K.J. / Wu, S.C. / Zhao, Z. / Adler, M. / Cheeseman, S. ...Authors: Ye, B. / Arnaiz, D.O. / Chou, Y.L. / Griedel, B.D. / Karanjawala, R. / Lee, W. / Morrissey, M.M. / Sacchi, K.L. / Sakata, S.T. / Shaw, K.J. / Wu, S.C. / Zhao, Z. / Adler, M. / Cheeseman, S. / Dole, W.P. / Ewing, J. / Fitch, R. / Lentz, D. / Liang, A. / Light, D. / Morser, J. / Post, J. / Rumennik, G. / Subramanyam, B. / Sullivan, M.E. / Vergona, R. / Walters, J. / Wang, Y.X. / White, K.A. / Whitlow, M. / Kochanny, M.J. #1: Journal: Biochemistry / Year: 2002 Title: Crystal Structures of Two Potent Nonamidine Inhibitors Bound to Factor Xa Authors: Adler, M. / Kochanny, M.J. / Bin, Y. / Rumennik, G. / Light, D.L. / Biancalana, S. / Whitlow, M. #2: Journal: Bioorg.Med.Chem. / Year: 2007 Title: Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa Authors: Kochanny, M.J. / Adler, M. / Ewing, J. / Griedel, B.D. / Ho, E. / Karanjawala, R. / Lee, W. / Lentz, D. / Liang, A.M. / Morrissey, M.M. / Phillips, G.B. / Post, J. / Sakata, K.L. / ...Authors: Kochanny, M.J. / Adler, M. / Ewing, J. / Griedel, B.D. / Ho, E. / Karanjawala, R. / Lee, W. / Lentz, D. / Liang, A.M. / Morrissey, M.M. / Phillips, G.B. / Post, J. / Sakata, K.L. / Subramanyam, B. / Vergona, R. / Walters, J. / White, K.A. / Whitlow, M. / Ye, B. / Zhao, Z. / Shaw, K.J. #3: Journal: Bioorg.Med.Chem.Lett. / Year: 2003 Title: Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors Authors: Chou, Y.L. / Davey, D.D. / Eagen, K.A. / Griedel, B.D. / Karanjawala, R. / Phillips, G.B. / Sacchi, K.L. / Shaw, K.J. / Wu, S.C. / Lentz, D. / Liang, A.M. / Trinh, L. / Morrissey, M.M. / Kochanny, M.J. #4: Journal: Biochemistry / Year: 2000 Title: Preparation, Characterization and the Crystal Structure of the Inhibitor ZK-807834 (Ci-1031) Complexed with Factor Xa Authors: Adler, M. / Davey, D.D. / Phillips, G.B. / Kim, S.H. / Jancarik, J. / Rumennik, G. / Light, D.L. / Whitlow, M. #5: Journal: J.Med.Chem. / Year: 2000 Title: Crystal Structures of Human Factor Xa Complexed with Potent Inhibitors Authors: Maignan, S. / Guilloteau, J.P. / Pouzieux, S. / Choi-Sledeski, Y.M. / Becker, M.R. / Klein, S.I. / Ewing, W.R. / Pauls, H.W. / Spada, A.P. / Mikol, V. #6: Journal: J.Med.Chem. / Year: 1998 Title: Discovery of N-[2-[5-[Amino(Imino)Methyl]-2-Hydroxyphenoxy]-3,5-Difluoro- 6-[3-(4,5-Dihydro-1-Methyl-1H-Imidazol-2-Yl)Phenoxy]Pyridin-4-Yl]-N-Methylglycine (Zk-807834): A Potent, Selective, ...Title: Discovery of N-[2-[5-[Amino(Imino)Methyl]-2-Hydroxyphenoxy]-3,5-Difluoro- 6-[3-(4,5-Dihydro-1-Methyl-1H-Imidazol-2-Yl)Phenoxy]Pyridin-4-Yl]-N-Methylglycine (Zk-807834): A Potent, Selective, and Orally Active Inhibitor of the Blood Coagulation Enzyme Factor Xa Authors: Phillips, G.B. / Buckman, B.O. / Davey, D.D. / Eagen, K.A. / Guilford, W.J. / Hinchman, J. / Ho, E. / Koovakkat, S. / Liang, A.M. / Light, D.R. / Mohan, R. / Ng, H.P. / Post, J.M. / Shaw, K. ...Authors: Phillips, G.B. / Buckman, B.O. / Davey, D.D. / Eagen, K.A. / Guilford, W.J. / Hinchman, J. / Ho, E. / Koovakkat, S. / Liang, A.M. / Light, D.R. / Mohan, R. / Ng, H.P. / Post, J.M. / Shaw, K.J. / Smith, D. / Subramanyam, B. / Sullivan, M.E. / Trinh, L. / Vergona, R. / Walters, J. / White, K. / Whitlow, M. / Wu, S. / Xu, W. / Morrissey, M.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2p3t.cif.gz | 77.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2p3t.ent.gz | 55.5 KB | Display | PDB format |
PDBx/mmJSON format | 2p3t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p3/2p3t ftp://data.pdbj.org/pub/pdb/validation_reports/p3/2p3t | HTTPS FTP |
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-Related structure data
Related structure data | 1fjsS 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: 5589.234 Da / Num. of mol.: 1 / Fragment: EGF-like 2 domain / Source method: isolated from a natural source / Details: EXTRACTED FROM BLOOD / Source: (natural) Homo sapiens (human) / References: UniProt: P00742 |
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#2: Protein | Mass: 26346.000 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN / Source method: isolated from a natural source / Details: EXTRACTED FROM BLOOD / Source: (natural) Homo sapiens (human) / References: UniProt: P00742, coagulation factor Xa |
-Non-polymers , 4 types, 175 molecules
#3: Chemical | ChemComp-CA / |
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#4: Chemical | ChemComp-CL / |
#5: Chemical | ChemComp-993 / |
#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: 2.44 Å3/Da / Density % sol: 51.2 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: A three-fold excess of the inhibitor was added to the DES-GLA-FACTOR XA. the protein was then concentrated to 12-17 MG/ML. Crystals were grown using 2 UL of complex with 2 UL of reservoir ...Details: A three-fold excess of the inhibitor was added to the DES-GLA-FACTOR XA. the protein was then concentrated to 12-17 MG/ML. Crystals were grown using 2 UL of complex with 2 UL of reservoir containing 15-21% PEG1500 and 10 MM CACL2, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 295K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 1.0332 |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Feb 24, 2000 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.92→50 Å / Num. obs: 25286 / % possible obs: 99.2 % / Observed criterion σ(I): -3 / Redundancy: 3.52 % / Biso Wilson estimate: 15 Å2 / Rsym value: 0.0749 / Net I/σ(I): 9.17 |
Reflection shell | Resolution: 1.92→2.04 Å / Redundancy: 3.57 % / Mean I/σ(I) obs: 1.76 / Rsym value: 0.3341 / % possible all: 100 |
-Processing
Software |
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Refinement | Starting model: PDB Entry 1FJS Resolution: 1.92→19.88 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 171365.35 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 54.0173 Å2 / ksol: 0.358387 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 28.1 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 1.92→19.88 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 6
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Xplor file |
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