[English] 日本語
Yorodumi- PDB-1c1u: RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1c1u | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASES | |||||||||
Components |
| |||||||||
Keywords | BLOOD CLOTTING/HYDROLASE INHIBITOR / ZN(II)-MEDIATED SERINE PROTEASE INHIBITORS / PH DEPENDENCE / ZN(II) AFFINITY STUCTURE-BASED DRUG DESIGN / SERINE PROTEASE/INHIBITOR / BLOOD CLOTTING-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 / DIFFERENCE FOURIER PLUS REFINEMENT / Resolution: 1.75 Å | |||||||||
Authors | Katz, B.A. / Luong, C. | |||||||||
Citation | Journal: Nature / Year: 1998 Title: Design of potent selective zinc-mediated serine protease inhibitors. Authors: Katz, B.A. / Clark, J.M. / Finer-Moore, J.S. / Jenkins, T.E. / Johnson, C.R. / Ross, M.J. / Luong, C. / Moore, W.R. / Stroud, R.M. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 1c1u.cif.gz | 152.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb1c1u.ent.gz | 119.7 KB | Display | PDB format |
PDBx/mmJSON format | 1c1u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c1/1c1u ftp://data.pdbj.org/pub/pdb/validation_reports/c1/1c1u | HTTPS FTP |
---|
-Related structure data
Related structure data | 1c1nC 1c1oC 1c1pC 1c1qC 1c1rC 1c1tC 1c1vC 1c1wC 1c2dC 1c2eC 1c2fC 1c2gC 1c2hC 1c2iC 1c2jC 1c2kC 1c2lC 1c2mC 1xufC 1xugC 1xuhC 1xuiC 1xujC 1xukC C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||
Unit cell |
| |||||||||
Components on special symmetry positions |
|
-Components
-Protein/peptide , 2 types, 2 molecules LI
#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) / References: UniProt: P00734, thrombin |
---|---|
#3: Protein/peptide | Mass: 1491.528 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28504 |
-Protein , 1 types, 1 molecules H
#2: Protein | Mass: 29780.219 Da / Num. of mol.: 1 / Fragment: HEAVY CHAIN / Source method: isolated from a natural source Details: COMPLEXED WITH (5-AMIDINO-2-BENZIMIDAZOLYL)(2-BENZIMIDAZOLYL)METHANE Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin |
---|
-Non-polymers , 4 types, 291 molecules
#4: Chemical | ChemComp-ZN / |
---|---|
#5: Chemical | ChemComp-NA / |
#6: Chemical | ChemComp-BAI / ( |
#7: Water | ChemComp-HOH / |
-Details
Compound details | HIS_H57 IS MONOPROTONATED ON THE DELTA NITROGEN. HIS_H91 AND HIS_H119 ARE MONOPROTONATED ON THE ...HIS_H57 IS MONOPROTON |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.62 Å3/Da / Density % sol: 36.7 % |
---|---|
Crystal grow | pH: 8.2 Details: THROMBIN WAS PURCHASED FROM HAEMATOLOGIC TECHNOLOGIES, INC. AND ACETYL-HIRUDIN FROM BACHEM. THROMBIN WAS PREPARED AS DESCRIBED (SKRZPCZAK-JANKUN ET AL., 1991) .THROMBIN (1.0 MG/ML IN 50 MM ...Details: THROMBIN WAS PURCHASED FROM HAEMATOLOGIC TECHNOLOGIES, INC. AND ACETYL-HIRUDIN FROM BACHEM. THROMBIN WAS PREPARED AS DESCRIBED (SKRZPCZAK-JANKUN ET AL., 1991) .THROMBIN (1.0 MG/ML IN 50 MM HEPES, 50 % GLYCEROL, PH 7.0) WAS INCUBATED WITH 1.0 MM ACETYL-HIRUDIN, 1.0 MM HEMI-BABIM, 1.0 MM ZN+2 FOR 1 HR AT 4 DEG C. GLYCEROL WAS REMOVED AND THE COMPLEX CONCENTRATED WITH A CENTRICON 10 ( AMICON) TO 8.6 MG/ML AS DETERMINED BY THE BIORAD PROTEIN ASSAY KIT USING BOVINE SERUM ALBUMIN. CRYSTALS OF THROMBIN-ACETYL-HIRUDIN-HEMI-BABIM-ZN+2 WERE GROWN IN HANGING DROPS BY VAPOR DIFFUSION AFTER STREAK SEEDING. THE DROPS WERE MADE FROM 5 MICROLITERS OF COMPLEX AND 5 MICROLITERS OF RESERVOIR SOLUTION ( 0.10 M TRIS,0.50 M NACL, 22 % (BY VOLUME) PEG 4K, PH 8.20). |
Crystal grow | *PLUS Method: unknown |
-Data collection
Diffraction | Mean temperature: 298 K |
---|---|
Diffraction source | Source: ROTATING ANODE / Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jan 23, 1998 / Details: MSC MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.45→38.78 Å / Num. obs: 35066 / % possible obs: 77 % / Observed criterion σ(I): 1 / Redundancy: 1.9 % / Rmerge(I) obs: 0.085 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 1.75→1.83 Å / Rmerge(I) obs: 0.25 / Mean I/σ(I) obs: 1.8 / % possible all: 50 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT Resolution: 1.75→7.5 Å / Cross valid method: X-PLOR / σ(F): 2 Details: BULK SOLVENT TERMS INCLUDED IN FOB FILE CREATED WITH STANDARD X-PLOR SCRIPT.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.75→7.5 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.75→1.83 Å / Total num. of bins used: 8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Xplor file | Serial no: 1 / Param file: PARMALLH3X_TH1706ZN.PRO / Topol file: TOPALLH6X_TH1706ZN.PRO |