|Entry||Database: PDB / ID: 1a4w|
|Title||CRYSTAL STRUCTURES OF THROMBIN WITH THIAZOLE-CONTAINING INHIBITORS: PROBES OF THE S1' BINDING SITE|
|Keywords||HYDROLASE/HYDROLASE INHIBITOR / SERINE PROTEASE-INHIBITOR / BLOOD COAGULATION / 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 / regulation of blood coagulation / cytolysis by host of symbiont cells / thrombospondin receptor activity / negative regulation of astrocyte differentiation / neutrophil mediated killing of gram-negative bacterium / thrombin / negative regulation of cytokine production involved in inflammatory response / negative regulation of platelet activation ...positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / regulation of blood coagulation / cytolysis by host of symbiont cells / thrombospondin receptor activity / negative regulation of astrocyte differentiation / neutrophil mediated killing of gram-negative bacterium / thrombin / negative regulation of cytokine production involved in inflammatory response / negative regulation of platelet activation / negative regulation of fibrinolysis / positive regulation of collagen biosynthetic process / positive regulation of blood coagulation / blood coagulation, intrinsic pathway / regulation of cytosolic calcium ion concentration / enzyme activator activity / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of release of sequestered calcium ion into cytosol / fibrinolysis / lipopolysaccharide binding / regulation of complement activation / acute-phase response / negative regulation of proteolysis / response to wounding / positive regulation of protein localization to nucleus / growth factor activity / positive regulation of reactive oxygen species metabolic process / serine-type endopeptidase inhibitor activity / Golgi lumen / platelet activation / endoplasmic reticulum to Golgi vesicle-mediated transport / leukocyte migration / positive regulation of phosphatidylinositol 3-kinase signaling / heparin binding / positive regulation of cell growth / regulation of cell shape / regulation of gene expression / cell surface receptor signaling pathway / blood microparticle / antimicrobial humoral immune response mediated by antimicrobial peptide / multicellular organism development / blood coagulation / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / signaling receptor binding / proteolysis / serine-type endopeptidase activity / cellular protein metabolic process / positive regulation of cell population proliferation / calcium ion binding / cell / extracellular space / extracellular exosome / extracellular region / plasma membrane
Peptidase S1, PA clan / Hirudin/antistatin / Kringle / Gamma-carboxyglutamic acid-rich (GLA) domain / Proteinase inhibitor I14, hirudin / Serine proteases, trypsin domain / Peptidase S1A, chymotrypsin family / Prothrombin/thrombin / Kringle-like fold / Kringle, conserved site ...Peptidase S1, PA clan / Hirudin/antistatin / Kringle / Gamma-carboxyglutamic acid-rich (GLA) domain / Proteinase inhibitor I14, hirudin / Serine proteases, trypsin domain / Peptidase S1A, chymotrypsin family / Prothrombin/thrombin / Kringle-like fold / Kringle, conserved site / Serine proteases, trypsin family, histidine active site / Thrombin light chain / Serine proteases, trypsin family, serine active site / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Thrombin light chain domain superfamily / Kringle superfamily / Trypsin / Trypsin-like serine proteases / Thrombin, subunit H / Beta Barrel / Mainly Beta
Prothrombin / Hirudin variant-2 / RWJ-50215
|Biological species||Homo sapiens (human)|
|Method||X-RAY DIFFRACTION / PREVIOUS STRUCTURE / Resolution: 1.8 Å|
|Authors||Matthews, J.H. / Krishnan, R. / Costanzo, M.J. / Maryanoff, B.E. / Tulinsky, A.|
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.
#1: Journal: Protein Sci. / Year: 1994
Title: The Isomorphous Structures of Prethrombin2, Hirugen-, and Ppack-Thrombin: Changes Accompanying Activation and Exosite Binding to Thrombin
Authors: Vijayalakshmi, J. / Padmanabhan, K.P. / Mann, K.G. / Tulinsky, A.
#2: Journal: Blood Coagulation Fibrinolysis / Year: 1993
Title: Active Site and Exosite Binding of Alpha-Thrombin
Authors: Tulinsky, A. / Qiu, X.
SummaryFull reportAbout validation report
|Structure viewer||Molecule: |
Downloads & links
L: ALPHA-THROMBIN (SMALL SUBUNIT)
H: ALPHA-THROMBIN (LARGE SUBUNIT)
-ALPHA-THROMBIN ... , 2 types, 2 molecules L
|#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
|#2: Protein/peptide|| |
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 genetically manipulated source
References: UniProt: P09945
-Non-polymers , 3 types, 160 molecules
|#4: Chemical||#5: Chemical|| ChemComp-QWE / ||#6: Water|| ChemComp-HOH / |
|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|
|Experiment||Method: X-RAY DIFFRACTION / Number of used crystals: 1|
|Crystal||Density Matthews: 2.4 Å3/Da / Density % sol: 51 %|
|Crystal grow||Method: vapor diffusion - hanging drop, macroseeding / pH: 7.3 |
Details: 0.1 M SODIUM PHOSPHATE BUFFER AT PH 7.3, 27-28% PEG 8000; HANGING DROPS WITH MACROSEEDING, vapor diffusion - hanging drop and macroseeding
*PLUSMethod: vapor diffusion, hanging drop / Details: Skrzypczak, J., (1991) J. Mol. Biol., 221, 1379.
|Components of the solutions|
|Diffraction||Mean temperature: 298 K|
|Diffraction source||Source: ROTATING ANODE / Type: RIGAKU RUH2R / Wavelength: 1.5418|
|Detector||Type: RIGAKU RAXIS II / Detector: IMAGE PLATE / Date: Mar 15, 1994 / 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||Resolution: 1.8→44.2 Å / Num. obs: 23968 / % possible obs: 69.5 % / Observed criterion σ(I): 1 / Redundancy: 2.2 % / Rmerge(I) obs: 0.052 / Net I/σ(I): 12|
|Reflection shell||Resolution: 1.8→2 Å / Rmerge(I) obs: 0.165 / Mean I/σ(I) obs: 2.61 / % possible all: 48|
*PLUSNum. measured all: 52463
|Refinement||Method to determine structure: PREVIOUS STRUCTURE|
Starting model: PDB ENTRY 1FPC
Resolution: 1.8→7 Å / σ(F): 4
|Displacement parameters||Biso mean: 26 Å2|
|Refinement step||Cycle: LAST / Resolution: 1.8→7 Å|
|Refine LS restraints|
Refinement-ID: X-RAY DIFFRACTION
*PLUSName: PROFFT / Classification: refinement
*PLUSRfactor obs: 0.155
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