[English] 日本語
Yorodumi- PDB-1gj4: SELECTIVITY AT S1, H2O DISPLACEMENT, UPA, TPA, SER190/ALA190 PROT... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1gj4 | ||||||
---|---|---|---|---|---|---|---|
Title | SELECTIVITY AT S1, H2O DISPLACEMENT, UPA, TPA, SER190/ALA190 PROTEASE, STRUCTURE-BASED DRUG DESIGN | ||||||
Components |
| ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / three-centered / very short hydrogen bond / oxyanion hole water / shift of pKa of His57 / structure-based drug design / specificity / urokinase / trypsin / thrombin / Zn+2-mediated inhibition / BLOOD CLOTTING / hydrolase / 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 / Resolution: 1.81 Å | ||||||
Authors | Katz, B.A. / Sprengeler, P.A. / Luong, C. / Verner, E. / Spencer, J.R. / Breitenbucher, J.G. / Hui, H. / McGee, D. / Allen, D. / Martelli, A. / Mackman, R.L. | ||||||
Citation | Journal: Chem.Biol. / Year: 2001 Title: Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets. Authors: Katz, B.A. / Sprengeler, P.A. / Luong, C. / Verner, E. / Elrod, K. / Kirtley, M. / Janc, J. / Spencer, J.R. / Breitenbucher, J.G. / Hui, H. / McGee, D. / Allen, D. / Martelli, A. / Mackman, R.L. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 1gj4.cif.gz | 147.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb1gj4.ent.gz | 117.8 KB | Display | PDB format |
PDBx/mmJSON format | 1gj4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1gj4_validation.pdf.gz | 715.1 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 1gj4_full_validation.pdf.gz | 723.5 KB | Display | |
Data in XML | 1gj4_validation.xml.gz | 18.7 KB | Display | |
Data in CIF | 1gj4_validation.cif.gz | 26.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gj/1gj4 ftp://data.pdbj.org/pub/pdb/validation_reports/gj/1gj4 | HTTPS FTP |
-Related structure data
Related structure data | 1gj5C 1gj6C 1gj7C 1gj8C 1gj9C 1gjaC 1gjbC 1gjcC 1gjdC C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||
Unit cell |
|
-Components
-Protein/peptide , 2 types, 2 molecules LI
#1: Protein/peptide | Mass: 4096.534 Da / Num. of mol.: 1 / Fragment: LIGHT CHAIN, RESIDUES 328-363 / 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: 29651.105 Da / Num. of mol.: 1 / Fragment: HEAVY CHAIN, RESIDUES 364-620 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin |
---|
-Non-polymers , 3 types, 271 molecules
#4: Chemical | ChemComp-NA / |
---|---|
#5: Chemical | ChemComp-132 / |
#6: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.61 Å3/Da / Density % sol: 52.85 % | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 7.8 Details: PEG 4000, NaCl (soak at pH 9.0), vapor diffusion at 298K, pH 7.8 | |||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS pH: 7.5 / Method: vapor diffusion, hanging dropDetails: used seeding, Katz, B.A., (2000) Chem.Biol., 7, 299. | |||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
|
-Data collection
Diffraction | Mean temperature: 298 K |
---|---|
Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Dec 1, 2000 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.56→44.03 Å / Num. all: 52398 / Num. obs: 23025 / % possible obs: 43.9 % / Observed criterion σ(I): 0.8 / Redundancy: 1.8 % / Rmerge(I) obs: 0.096 / Net I/σ(I): 5 |
Reflection shell | Resolution: 1.8→1.85 Å / Rmerge(I) obs: 0.262 / Num. unique all: 853 / % possible all: 32.2 |
Reflection | *PLUS Num. obs: 19152 |
Reflection shell | *PLUS Highest resolution: 1.81 Å / Lowest resolution: 1.89 Å |
-Processing
Software |
| ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Resolution: 1.81→7 Å / σ(F): 1.75 / Stereochemistry target values: X-PLOR force field Details: Met_H84, Met_H106, Arg_H126, and Pro_H166 were simultaneously refined in two conformations. No density was observed for Trp148, Thr149, Ala149A, Asn149B, Val149C, Gly149D, and Lys149E in the ...Details: Met_H84, Met_H106, Arg_H126, and Pro_H166 were simultaneously refined in two conformations. No density was observed for Trp148, Thr149, Ala149A, Asn149B, Val149C, Gly149D, and Lys149E in the autolysis loop, and these residues are not included in the model. No density was observed for C-terminal residues of the heavy chain following Gly_H246. Residues after Gly_H246 are not included in the model. Likewise, only the residue from Glu_L1C through L14K are included for the light chain. In the non-active site peptide inhibitor (acetylhirudin) the tyrosine hydroxyl is sulfonated. HOH753 makes a short hydrogen bond with OgSer195 and with O6' of the inhibitor Disordered waters include: HOH395 is close to a symmetry related equivalent of itself; HOH396 is close to a symmetry related equivalent of itself; HOH397 is close to a symmetry related equivalent of itself. The above "waters" correspond to density that is more electron dense than waters. The occupancies were allowed to refine to values greater than unity. HOH524 which is close to HOH525; HOH579 which is close to HOH580; HOH624 which is close to HOH625, which in turn is close to HOH626; HOH877 which is close to a symmetry-related equivalent of itself. HIS_H57 IS doubly protonated. HIS_H91 and His_H119 are MONOPROTONATED ON the epsilon nitrogen
| ||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.81→7 Å
| ||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||
Refinement | *PLUS Highest resolution: 2 Å / Rfactor all: 0.207 / Rfactor obs: 0.187 / Rfactor Rwork: 0.187 | ||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||
LS refinement shell | *PLUS Highest resolution: 1.81 Å / Lowest resolution: 1.89 Å / Rfactor Rwork: 0.207 / Rfactor obs: 0.207 |