+Open data
-Basic information
Entry | Database: PDB / ID: 1mu8 | ||||||
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Title | thrombin-hirugen_l-378,650 | ||||||
Components |
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Keywords | HYDROLASE/HYDROLASE INHIBITOR / thrombin-hirugen / BLOOD CLOTTING / 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 / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / 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 / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of platelet activation / negative regulation of astrocyte differentiation / 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 / fibrinolysis / regulation of cytosolic calcium ion concentration / Intrinsic Pathway of Fibrin Clot Formation / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / Regulation of Complement cascade / acute-phase response / Cell surface interactions at the vascular wall / lipopolysaccharide binding / negative regulation of proteolysis / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / platelet activation / response to wounding / Golgi lumen / positive regulation of protein localization to nucleus / 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 / blood coagulation / antimicrobial humoral immune response mediated by antimicrobial peptide / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / regulation of cell shape / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / blood microparticle / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / signaling receptor binding / serine-type endopeptidase activity / calcium ion binding / positive regulation of cell population proliferation / 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 / FOURIER SYNTHESIS / Resolution: 2 Å | ||||||
Authors | Burgey, C.S. / Robinson, K.A. / Lyle, T.A. / Sanderson, P.E. / Lewis, S.D. / Lucas, B.J. / Krueger, J.A. / Singh, R. / Miller-Stein, C. / White, R.B. ...Burgey, C.S. / Robinson, K.A. / Lyle, T.A. / Sanderson, P.E. / Lewis, S.D. / Lucas, B.J. / Krueger, J.A. / Singh, R. / Miller-Stein, C. / White, R.B. / Wong, B. / Lyle, E.A. / Williams, P.D. / Coburn, C.A. / Dorsey, B.D. / Barrow, J.C. / Stranieri, M.T. / Holahan, M.A. / Sitko, G.R. / Cook, J.J. / McMasters, D.R. / McDonough, C.M. / Sanders, W.M. / Wallace, A.A. / Clayton, F.C. / Bohn, D. / Leonard, Y.M. / Detwiler Jr., T.J. / Lynch Jr., J.J. / Yan, Y. / Chen, Z. / Kuo, L. / Gardell, S.J. / Shafer, J.A. / Vacca, J.P.J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2003 Title: Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines. Authors: Burgey, C.S. / Robinson, K.A. / Lyle, T.A. / Sanderson, P.E. / Lewis, S.D. / Lucas, B.J. / Krueger, J.A. / Singh, R. / Miller-Stein, C. / White, R.B. / Wong, B. / Lyle, E.A. / Williams, P.D. ...Authors: Burgey, C.S. / Robinson, K.A. / Lyle, T.A. / Sanderson, P.E. / Lewis, S.D. / Lucas, B.J. / Krueger, J.A. / Singh, R. / Miller-Stein, C. / White, R.B. / Wong, B. / Lyle, E.A. / Williams, P.D. / Coburn, C.A. / Dorsey, B.D. / Barrow, J.C. / Stranieri, M.T. / Holahan, M.A. / Sitko, G.R. / Cook, J.J. / McMasters, D.R. / McDonough, C.M. / Sanders, W.M. / Wallace, A.A. / Clayton, F.C. / Bohn, D. / Leonard, Y.M. / Detwiler Jr., T.J. / Lynch Jr., J.J. / Yan, Y. / Chen, Z. / Kuo, L. / Gardell, S.J. / Shafer, J.A. / Vacca, J.P.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1mu8.cif.gz | 70.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1mu8.ent.gz | 55.7 KB | Display | PDB format |
PDBx/mmJSON format | 1mu8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mu/1mu8 ftp://data.pdbj.org/pub/pdb/validation_reports/mu/1mu8 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein/peptide | Mass: 4096.534 Da / Num. of mol.: 1 / Fragment: light chain / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: plasma / References: UniProt: P00734, thrombin |
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#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Fragment: heavy chain / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: plasma / References: UniProt: P00734, thrombin |
#3: Protein/peptide | Mass: 1491.528 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: This peptide was chemically synthesized. It is naturally found in Hirudo medicinalis (Medicinal leech). Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28506 |
#4: Chemical | ChemComp-CDB / |
#5: 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: 2.6 Å3/Da / Density % sol: 52.76 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7.3 Details: pH 7.3, VAPOR DIFFUSION, HANGING DROP, temperature 295K |
-Data collection
Diffraction | Mean temperature: 290 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS II / Detector: IMAGE PLATE / Date: 1998 / Details: mirrors |
Radiation | Monochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2→25 Å / Num. all: 24639 / Num. obs: 23202 / % possible obs: 94.2 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 |
Reflection shell | Resolution: 2→25.942 Å |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2→25 Å / Cross valid method: FREE R-VALUE / σ(F): 0 / σ(I): 0
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Refinement step | Cycle: LAST / Resolution: 2→25 Å
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