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Yorodumi- PDB-7pr7: Crystal structure of human heparanase in complex with covalent in... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7pr7 | ||||||||||||||||||||||||
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Title | Crystal structure of human heparanase in complex with covalent inhibitor VL166 | ||||||||||||||||||||||||
Components |
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Keywords | CARBOHYDRATE / glycoside hydrolase / glucuronidase / GH79 / heparan sulfate | ||||||||||||||||||||||||
Function / homology | Function and homology information heparanase / heparanase activity / regulation of hair follicle development / heparin metabolic process / proteoglycan metabolic process / heparan sulfate proteoglycan catabolic process / beta-glucuronidase activity / positive regulation of hair follicle development / HS-GAG degradation / syndecan binding ...heparanase / heparanase activity / regulation of hair follicle development / heparin metabolic process / proteoglycan metabolic process / heparan sulfate proteoglycan catabolic process / beta-glucuronidase activity / positive regulation of hair follicle development / HS-GAG degradation / 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 / extracellular matrix / cell-matrix adhesion / : / specific granule lumen / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / lysosome / 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: 1.52 Å | ||||||||||||||||||||||||
Authors | Wu, L. / Armstrong, Z. / Davies, G.J. | ||||||||||||||||||||||||
Funding support | United Kingdom, 7items
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Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2022 Title: Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo. Authors: de Boer, C. / Armstrong, Z. / Lit, V.A.J. / Barash, U. / Ruijgrok, G. / Boyango, I. / Weitzenberg, M.M. / Schroder, S.P. / Sarris, A.J.C. / Meeuwenoord, N.J. / Bule, P. / Kayal, Y. / Ilan, N. ...Authors: de Boer, C. / Armstrong, Z. / Lit, V.A.J. / Barash, U. / Ruijgrok, G. / Boyango, I. / Weitzenberg, M.M. / Schroder, S.P. / Sarris, A.J.C. / Meeuwenoord, N.J. / Bule, P. / Kayal, Y. / Ilan, N. / Codee, J.D.C. / Vlodavsky, I. / Overkleeft, H.S. / Davies, G.J. / Wu, L. | ||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7pr7.cif.gz | 211.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pr7.ent.gz | 163.3 KB | Display | PDB format |
PDBx/mmJSON format | 7pr7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pr/7pr7 ftp://data.pdbj.org/pub/pdb/validation_reports/pr/7pr7 | HTTPS FTP |
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-Related structure data
Related structure data | 7pr6C 7pr8C 7pr9C 7prbC 7prtC 7pshC 7psiC 7psjC 7pskC 5e8mS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 43334.898 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 |
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#2: Protein | Mass: 8273.514 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 |
-Sugars , 3 types, 5 molecules
#3: Polysaccharide | alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#4: Polysaccharide | 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-(2R,3S,5R,6R)-2,3,4,5,6-pentakis(oxidanyl) ...2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-(2R,3S,5R,6R)-2,3,4,5,6-pentakis(oxidanyl)cyclohexane-1-carboxylic acid Type: oligosaccharide / Mass: 411.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
#5: Sugar |
-Non-polymers , 3 types, 332 molecules
#6: Chemical | ChemComp-EDO / #7: Chemical | ChemComp-CL / | #8: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.52 Å3/Da / Density % sol: 51.17 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5.5 / Details: 0.1 M MES pH 5.5, 0.1 M MgCl2, 17% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97933 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 30, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97933 Å / Relative weight: 1 |
Reflection | Resolution: 1.52→52.78 Å / Num. obs: 78665 / % possible obs: 99.9 % / Redundancy: 4.1 % / CC1/2: 0.998 / Rmerge(I) obs: 0.051 / Rpim(I) all: 0.028 / Net I/σ(I): 12.3 |
Reflection shell | Resolution: 1.52→1.56 Å / Redundancy: 4.1 % / Rmerge(I) obs: 1.341 / Mean I/σ(I) obs: 1.1 / Num. unique obs: 5772 / CC1/2: 0.479 / Rpim(I) all: 0.741 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5e8m Resolution: 1.52→46.256 Å / Cor.coef. Fo:Fc: 0.978 / Cor.coef. Fo:Fc free: 0.971 / WRfactor Rfree: 0.2 / WRfactor Rwork: 0.175 / SU B: 1.795 / SU ML: 0.061 / Average fsc free: 0.8827 / Average fsc work: 0.8871 / Cross valid method: FREE R-VALUE / ESU R: 0.068 / ESU R Free: 0.068 Details: Hydrogens have been added in their riding positions
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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: 33.372 Å2
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Refinement step | Cycle: LAST / Resolution: 1.52→46.256 Å
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Refine LS restraints |
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LS refinement shell |
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