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Yorodumi- PDB-1a46: THROMBIN COMPLEXED WITH HIRUGEN AND A BETA-STRAND MIMETIC INHIBITOR -
+Open data
-Basic information
Entry | Database: PDB / ID: 1a46 | ||||||
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Title | THROMBIN COMPLEXED WITH HIRUGEN AND A BETA-STRAND MIMETIC INHIBITOR | ||||||
Components |
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Keywords | HYDROLASE/HYDROLASE INHIBITOR / COMPLEX (SERINE PROTEASE-INHIBITOR) / HYDROLASE-HYDROLASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin ...positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / negative regulation of platelet activation / positive regulation of collagen biosynthetic process / negative regulation of cytokine production involved in inflammatory response / positive regulation of blood coagulation / negative regulation of fibrinolysis / 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 / regulation of cytosolic calcium ion concentration / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / acute-phase response / Regulation of Complement cascade / negative regulation of proteolysis / Cell surface interactions at the vascular wall / lipopolysaccharide binding / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / positive regulation of insulin secretion / platelet activation / response to wounding / positive regulation of protein localization to nucleus / Golgi lumen / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of reactive oxygen species metabolic process / serine-type endopeptidase inhibitor activity / antimicrobial humoral immune response mediated by antimicrobial peptide / blood coagulation / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / positive regulation of cell growth / regulation of cell shape / G alpha (q) signalling events / collagen-containing extracellular matrix / blood microparticle / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / positive regulation of cell population proliferation / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Hirudo medicinalis (medicinal leech) | ||||||
Method | X-RAY DIFFRACTION / PREVIOUS STRUCTURE / Resolution: 2.12 Å | ||||||
Authors | St Charles, R. / Matthews, J.H. / Zhang, E. / Tulinsky, A. / Kahn, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 1999 Title: Bound structures of novel P3-P1' beta-strand mimetic inhibitors of thrombin. Authors: St Charles, R. / Matthews, J.H. / Zhang, E. / Tulinsky, A. #1: Journal: Biophys.J. / Year: 1996 Title: Crystal Structures of Thrombin with Thiazole-Containing Inhibitors: Probes of the S1' Binding Site Authors: Matthews, J.H. / Krishnan, R. / Costanzo, M.J. / Maryanoff, B.E. / Tulinsky, A. #2: Journal: Protein Eng. / Year: 1993 Title: The Structure of a Designed Peptidomimetic Inhibitor Complex of Alpha-Thrombin Authors: Wu, T.P. / Yee, V. / Tulinsky, A. / Chrusciel, R.A. / Nakanishi, H. / Shen, R. / Priebe, C. / Kahn, M. #3: Journal: Blood Coagulation Fibrinolysis / Year: 1993 Title: Active Site and Exosite Binding of Alpha-Thrombin Authors: Tulinsky, A. / Qiu, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1a46.cif.gz | 75.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1a46.ent.gz | 57.4 KB | Display | PDB format |
PDBx/mmJSON format | 1a46.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1a46_validation.pdf.gz | 807.5 KB | Display | wwPDB validaton report |
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Full document | 1a46_full_validation.pdf.gz | 821.7 KB | Display | |
Data in XML | 1a46_validation.xml.gz | 17.8 KB | Display | |
Data in CIF | 1a46_validation.cif.gz | 24.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a4/1a46 ftp://data.pdbj.org/pub/pdb/validation_reports/a4/1a46 | HTTPS FTP |
-Related structure data
Related structure data | 1a5gC 1a61C 1b5gC 1hahS S: Starting model for refinement C: citing same article (ref.) |
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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
-ALPHA-THROMBIN ... , 2 types, 2 molecules LH
#1: Protein/peptide | Mass: 4096.534 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Organ: BLOOD / Tissue: BLOOD / References: UniProt: P00734, thrombin |
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#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Organ: BLOOD / Tissue: BLOOD / References: UniProt: P00734, thrombin |
-Protein/peptide , 1 types, 1 molecules I
#3: Protein/peptide | Mass: 1534.554 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Hirudo medicinalis (medicinal leech) / References: UniProt: P09945 |
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-Non-polymers , 3 types, 168 molecules
#4: Chemical | #5: Chemical | ChemComp-00K / ( | #6: Water | ChemComp-HOH / | |
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-Details
Compound details | THROMBIN IS CLEAVED BETWEEN RESIDUES 15 AND 16. CHAIN IDENTIFIER *L* IS USED FOR RESIDUES 1H - 15 ...THROMBIN IS CLEAVED BETWEEN RESIDUES 15 AND 16. CHAIN IDENTIFIER |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.4 Å3/Da / Density % sol: 51 % | ||||||||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | Method: vapor diffusion - hanging drop, macroseeding / pH: 7.3 Details: 0.1 M SODIUM PHOSPHATE BUFFER, PH 7.3, 27-28 % PEG 8000, HANGING DROPS AND MACROSEEDING; THEN SOAKED IN PEG-PHOSPHATE-0.1 M NACL, AND THE MOL 106 INHIBITOR WAS ADDED IN 3 STEPS WITH FINAL ...Details: 0.1 M SODIUM PHOSPHATE BUFFER, PH 7.3, 27-28 % PEG 8000, HANGING DROPS AND MACROSEEDING; THEN SOAKED IN PEG-PHOSPHATE-0.1 M NACL, AND THE MOL 106 INHIBITOR WAS ADDED IN 3 STEPS WITH FINAL CONC. 7.3 MM, vapor diffusion - hanging drop and macroseeding | ||||||||||||||||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS Method: vapor diffusion, hanging drop / Details: Skrzypczak, J., (1991) J. Mol. Biol., 221, 1379. | ||||||||||||||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 298 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH2R / Wavelength: 1.5418 |
Detector | Type: SIEMENS / Detector: AREA DETECTOR / Date: May 15, 1995 / Details: COLLIMATOR |
Radiation | Monochromator: GRAPHITE(002) / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Highest resolution: 2.12 Å / Num. obs: 18219 / % possible obs: 86 % / Redundancy: 3 % / Rmerge(I) obs: 0.044 / Net I/σ(I): 23.8 |
Reflection shell | Resolution: 2.12→2.26 Å / Redundancy: 1.7 % / Rmerge(I) obs: 0.229 / Mean I/σ(I) obs: 3.5 / % possible all: 60 |
Reflection | *PLUS Num. measured all: 54609 |
Reflection shell | *PLUS % possible obs: 60 % |
-Processing
Software |
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Refinement | Method to determine structure: PREVIOUS STRUCTURE Starting model: PDB ENTRY 1HAH Resolution: 2.12→7 Å / σ(F): 4
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Displacement parameters | Biso mean: 24 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.12→7 Å
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Refine LS restraints |
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Software | *PLUS Name: PROFFT / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | *PLUS Rfactor obs: 0.155 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | *PLUS |