+Open data
-Basic information
Entry | Database: PDB / ID: 8jyg | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of Human HPSE1 in complex with inhibitor | ||||||
Components |
| ||||||
Keywords | HYDROLASE/INHIBITOR / Endo-glucoronidase / Heparanase-1 / HEP / HPA / HPA1 / HPR1 / HPSE1 / HSE1 / HYDROLASE / HYDROLASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information heparanase / heparanase activity / regulation of hair follicle development / heparan sulfate proteoglycan catabolic process / heparin metabolic process / proteoglycan metabolic process / HS-GAG degradation / positive regulation of hair follicle development / beta-glucuronidase activity / syndecan binding ...heparanase / heparanase activity / regulation of hair follicle development / heparan sulfate proteoglycan catabolic process / heparin metabolic process / proteoglycan metabolic process / HS-GAG degradation / positive regulation of hair follicle development / beta-glucuronidase activity / syndecan binding / protein transmembrane transport / vascular wound healing / angiogenesis involved in wound healing / establishment of endothelial barrier / positive regulation of osteoblast proliferation / positive regulation of vascular endothelial growth factor production / positive regulation of blood coagulation / lysosomal lumen / cell-matrix adhesion / extracellular matrix / specific granule lumen / lysosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / membrane raft / lysosomal membrane / intracellular membrane-bounded organelle / Neutrophil degranulation / extracellular space / extracellular region / nucleoplasm / nucleus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å | ||||||
Authors | Mima, M. / Fujimoto, N. / Imai, Y. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2023 Title: Structure-based lead optimization to improve potency and selectivity of a novel tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid series of heparanase-1 inhibitor. Authors: Imai, Y. / Suzuki, R. / Wakasugi, D. / Matsuda, D. / Tanaka-Yamamoto, N. / Ohki, Y. / Mima, M. / Endo, M. / Tabata, R. / Matsuzawa, H. / Hasegawa, Y. / Kato, S. / Sugisaki, M. / Miyagawa, H. ...Authors: Imai, Y. / Suzuki, R. / Wakasugi, D. / Matsuda, D. / Tanaka-Yamamoto, N. / Ohki, Y. / Mima, M. / Endo, M. / Tabata, R. / Matsuzawa, H. / Hasegawa, Y. / Kato, S. / Sugisaki, M. / Miyagawa, H. / Fujimoto, N. / Fukunaga, T. / Kato, S. / Takahashi, T. / Kakinuma, H. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8jyg.cif.gz | 120.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8jyg.ent.gz | 85.9 KB | Display | PDB format |
PDBx/mmJSON format | 8jyg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8jyg_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8jyg_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8jyg_validation.xml.gz | 21.8 KB | Display | |
Data in CIF | 8jyg_validation.cif.gz | 31.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jy/8jyg ftp://data.pdbj.org/pub/pdb/validation_reports/jy/8jyg | HTTPS FTP |
-Related structure data
Related structure data | 5e8mS S: Starting model for refinement |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 43464.074 Da / Num. of mol.: 1 / Mutation: K307R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9Y251, heparanase |
---|---|
#2: Protein | Mass: 8415.670 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9Y251, heparanase |
-Sugars , 1 types, 2 molecules
#5: Sugar |
---|
-Non-polymers , 3 types, 231 molecules
#3: Chemical | ChemComp-V8R / ( | ||
---|---|---|---|
#4: Chemical | ChemComp-EDO / #6: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.36 Å3/Da / Density % sol: 47.77 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 5.5 Details: 25% w/v Polyethylene glycol 3,350, 100 mM BIS-TRIS pH 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00003 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 10, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.00003 Å / Relative weight: 1 |
Reflection | Resolution: 2→77.5 Å / Num. obs: 32623 / % possible obs: 99.8 % / Redundancy: 5.3 % / CC1/2: 0.993 / Net I/σ(I): 7.5 |
Reflection shell | Resolution: 2→2.05 Å / Num. unique obs: 2388 / CC1/2: 0.79 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5E8M Resolution: 2→43.977 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.951 / SU B: 4.914 / SU ML: 0.128 / Cross valid method: THROUGHOUT / ESU R: 0.174 / ESU R Free: 0.153 Details: Hydrogens have been added in their riding positions
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.783 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2→43.977 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|