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Yorodumi- PDB-1dwb: CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BIND... -
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-Basic information
Entry | Database: PDB / ID: 1dwb | ||||||
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Title | CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS | ||||||
Components |
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Keywords | HYDROLASE/HYDROLASE INHIBITOR / SERINE PROTEINASE / 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 / ligand-gated ion channel signaling pathway / neutrophil-mediated killing of gram-negative bacterium / 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 / ligand-gated ion channel signaling pathway / neutrophil-mediated killing of gram-negative bacterium / 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 / 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 / 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 / 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 / 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 / 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 / Resolution: 3.16 Å | ||||||
Authors | Banner, D.W. / Hadvary, P. | ||||||
Citation | Journal: J.Biol.Chem. / Year: 1991 Title: Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors. Authors: Banner, D.W. / Hadvary, P. #1: Journal: Eur.J.Biochem. / Year: 1990 Title: Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3- ...Title: Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin. Authors: Bode, W. / Turk, D. / Sturzebecher, J. #2: Journal: Embo J. / Year: 1989 Title: The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. Authors: Bode, W. / Mayr, I. / Baumann, U. / Huber, R. / Stone, S.R. / Hofsteenge, J. #3: Journal: Protein Sci. / Year: 1992 Title: The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active- ...Title: The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Authors: Bode, W. / Turk, D. / Karshikov, A. #4: Journal: Science / Year: 1990 Title: The structure of a complex of recombinant hirudin and human alpha-thrombin. Authors: Rydel, T.J. / Ravichandran, K.G. / Tulinsky, A. / Bode, W. / Huber, R. / Roitsch, C. / Fenton, J.W. #5: Journal: Eur.J.Biochem. / Year: 1992 Title: The interaction of thrombin with fibrinogen. A structural basis for its specificity. Authors: Stubbs, M.T. / Oschkinat, H. / Mayr, I. / Huber, R. / Angliker, H. / Stone, S.R. / Bode, W. #6: Journal: Embo J. / Year: 1990 Title: Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition. Authors: Grutter, M.G. / Priestle, J.P. / Rahuel, J. / Grossenbacher, H. / Bode, W. / Hofsteenge, J. / Stone, S.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1dwb.cif.gz | 73 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1dwb.ent.gz | 54.1 KB | Display | PDB format |
PDBx/mmJSON format | 1dwb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dw/1dwb ftp://data.pdbj.org/pub/pdb/validation_reports/dw/1dwb | 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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Atom site foot note | 1: CIS PROLINE - PRO H 37 2: PHE H 245 - GLY H 246 OMEGA = 0.00 PEPTIDE BOND DEVIATES SIGNIFICANTLY FROM TRANS CONFORMATION 3: LEU I 10 - GLN I 11 OMEGA =359.98 PEPTIDE BOND DEVIATES SIGNIFICANTLY FROM TRANS CONFORMATION 4: RESIDUE ASN H 60G IS GLYCOSYLATED. THE SUGAR ELECTRON DENSITY IS WEAK AND NO COORDINATES ARE PRESENT FOR THE SUGAR. |
-Components
#1: Protein/peptide | Mass: 4096.534 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Organ: PLASMA / References: UniProt: P00734, thrombin |
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#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Organ: PLASMA / References: UniProt: P00734, thrombin |
#3: Protein/peptide | Mass: 1411.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28508, UniProt: P28504*PLUS |
#4: Chemical | ChemComp-BEN / |
#5: Water | ChemComp-HOH / |
Compound details | THROMBIN IS CLEAVED BETWEEN RESIDUES 15 AND 16. CHAIN INDICATOR *L* IS USED FOR RESIDUES 1H - 15 ...THROMBIN IS CLEAVED BETWEEN RESIDUES 15 AND 16. CHAIN INDICATOR *L* IS USED FOR RESIDUES 1H - 15 AND CHAIN INDICATOR *H* IS USED FOR RESIDUES 16 - 247. CHAIN INDICATOR *I* IS USED FOR A C-TERMINAL HIRUDIN PEPTIDE ((DES-AMINO ASP55)HIRUDIN(55-65)). THE RESIDUES OF CHAIN I ARE NUMBERED FROM 1 - 11. IT BINDS IN THE ANION-BINDING EXOSITE. |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.87 Å3/Da / Density % sol: 68.2 % | ||||||||||||||||||||||||||||||||||||
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Crystal grow | *PLUS pH: 7.5 / Method: vapor diffusion | ||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Radiation | Scattering type: x-ray |
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Radiation wavelength | Relative weight: 1 |
Reflection | *PLUS Highest resolution: 2.58 Å / Lowest resolution: 9999 Å / Num. obs: 10195 / Num. measured all: 19982 / Rmerge(I) obs: 0.069 |
-Processing
Software | Name: TNT / Classification: refinement | ||||||||||||||||||||||||||||||
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Refinement | Resolution: 3.16→25 Å / Rfactor obs: 0.151 / σ(F): 0 Details: PROLINES ARE TOO FLAT AS A BAD DICTIONARY WAS USED. ASN H 60G IS GLYCOSYLATED. THE SUGAR ELECTRON DENSITY IS WEAK AND NO COORDINATES ARE PRESENT FOR THE SUGAR. | ||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.16→25 Å
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Refine LS restraints |
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Refinement | *PLUS Highest resolution: 3.16 Å / Lowest resolution: 25 Å / σ(F): 0 / Rfactor all: 0.151 / Num. reflection all: 7477 | ||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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