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Yorodumi- PDB-6f5m: Crystal structure of highly glycosylated human leukocyte elastase... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6f5m | |||||||||
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Title | Crystal structure of highly glycosylated human leukocyte elastase in complex with a thiazolidinedione inhibitor | |||||||||
Components | Neutrophil elastase | |||||||||
Keywords | HYDROLASE / human leukocyte elastase / human neutrophil elastase / parabolic inhibition / glycosylation | |||||||||
Function / homology | Function and homology information leukocyte elastase / biosynthetic process of antibacterial peptides active against Gram-negative bacteria / neutrophil-mediated killing of fungus / acute inflammatory response to antigenic stimulus / negative regulation of chemotaxis / positive regulation of leukocyte tethering or rolling / response to yeast / leukocyte migration involved in inflammatory response / negative regulation of interleukin-8 production / negative regulation of chemokine production ...leukocyte elastase / biosynthetic process of antibacterial peptides active against Gram-negative bacteria / neutrophil-mediated killing of fungus / acute inflammatory response to antigenic stimulus / negative regulation of chemotaxis / positive regulation of leukocyte tethering or rolling / response to yeast / leukocyte migration involved in inflammatory response / negative regulation of interleukin-8 production / negative regulation of chemokine production / Antimicrobial peptides / pyroptotic inflammatory response / Activation of Matrix Metalloproteinases / neutrophil-mediated killing of gram-negative bacterium / cytokine binding / Collagen degradation / extracellular matrix disassembly / Pyroptosis / phagocytosis / response to UV / phagocytic vesicle / transcription repressor complex / Degradation of the extracellular matrix / secretory granule / Regulation of Complement cascade / positive regulation of interleukin-8 production / positive regulation of smooth muscle cell proliferation / positive regulation of MAP kinase activity / protein catabolic process / negative regulation of inflammatory response / intracellular calcium ion homeostasis / specific granule lumen / transcription corepressor activity / positive regulation of immune response / azurophil granule lumen / heparin binding / peptidase activity / protease binding / collagen-containing extracellular matrix / endopeptidase activity / response to lipopolysaccharide / defense response to bacterium / serine-type endopeptidase activity / Neutrophil degranulation / negative regulation of transcription by RNA polymerase II / cell surface / proteolysis / extracellular space / extracellular exosome / extracellular region / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | |||||||||
Authors | Hochscherf, J. / Pietsch, M. / Tieu, W. / Kuan, K. / Hautmann, S. / Abell, A. / Guetschow, M. / Niefind, K. | |||||||||
Funding support | Germany, 1items
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Citation | Journal: Acta Crystallogr F Struct Biol Commun / Year: 2018 Title: Crystal structure of highly glycosylated human leukocyte elastase in complex with an S2' site binding inhibitor. Authors: Hochscherf, J. / Pietsch, M. / Tieu, W. / Kuan, K. / Abell, A.D. / Gutschow, M. / Niefind, K. #1: Journal: J. Mol. Biol. / Year: 2011 Title: Unexpected active-site flexibility in the structure of human neutrophil elastase in complex with a new dihydropyrimidone inhibitor. Authors: Hansen, G. / Gielen-Haertwig, H. / Reinemer, P. / Schomburg, D. / Harrenga, A. / Niefind, K. #2: Journal: Bioorg. Med. Chem. Lett. / Year: 2012 Title: 5-benzylidenerhodanine and 5-benzylidene-2-4-thiazolidinedione based antibacterials. Authors: Zvarec, O. / Polyak, S.W. / Tieu, W. / Kuan, K. / Dai, H. / Pedersen, D.S. / Morona, R. / Zhang, L. / Booker, G.W. / Abell, A.D. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6f5m.cif.gz | 196.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6f5m.ent.gz | 159.2 KB | Display | PDB format |
PDBx/mmJSON format | 6f5m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f5/6f5m ftp://data.pdbj.org/pub/pdb/validation_reports/f5/6f5m | HTTPS FTP |
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-Related structure data
Related structure data | 1ppgS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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Components on special symmetry positions |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 23318.982 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08246, leukocyte elastase |
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-Sugars , 3 types, 4 molecules
#2: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||
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#3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source |
-Non-polymers , 4 types, 53 molecules
#5: Chemical | ChemComp-SO4 / #6: Chemical | #7: Chemical | #8: Water | ChemComp-HOH / | |
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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: 2.68 Å3/Da / Density % sol: 54.16 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: HLE from human blood was purchased from SERVA as a lyophilisate in the presence of sodium acetate puffer, pH 5.5. The lyophilisate was disolved in water so that the HLE concentration was 5 ...Details: HLE from human blood was purchased from SERVA as a lyophilisate in the presence of sodium acetate puffer, pH 5.5. The lyophilisate was disolved in water so that the HLE concentration was 5 mg/ml (170 micromolar) and the acetate concentration 250 millimolar. 120 microliter dissolved HNE lysophilisate was mixed with 6 microliter inhibitor solution (10 mM in DMSO). 1 microliter of the resulting HLE/inhibitor mixture was mixed with 0.5 microliter reservoir solution which was composed of 20 % PEG MME 5000, 0.2 M potassium sulphate. Repeated seeding was necessary to get usable crystals. In the final seeding step the reservoir was composed of 20 % PEG MME 5000, 0.2 M sodium sulphate. PH range: 5-7 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Oct 20, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→45.6 Å / Num. obs: 13722 / % possible obs: 99.94 % / Redundancy: 20.7 % / Biso Wilson estimate: 62.04 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.2407 / Rsym value: 0.2407 / Net I/σ(I): 15.4 |
Reflection shell | Resolution: 2.7→2.83 Å / Redundancy: 21.6 % / Mean I/σ(I) obs: 1.2 / Num. unique obs: 1808 / CC1/2: 0.442 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1PPG Resolution: 2.7→45.553 Å / SU ML: 0.36 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 26.83 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7→45.553 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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