+Open data
-Basic information
Entry | Database: PDB / ID: 6ela | ||||||
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Title | Crystal structure of MMP12 in complex with inhibitor BE4. | ||||||
Components | Macrophage metalloelastase | ||||||
Keywords | HYDROLASE / metzincin / carboxylate inhibitor alternative zinc-binding groups | ||||||
Function / homology | Function and homology information macrophage elastase / negative regulation of endothelial cell-matrix adhesion via fibronectin / bronchiole development / positive regulation of epithelial cell proliferation involved in wound healing / elastin catabolic process / regulation of defense response to virus by host / positive regulation of type I interferon-mediated signaling pathway / wound healing, spreading of epidermal cells / negative regulation of type I interferon-mediated signaling pathway / lung alveolus development ...macrophage elastase / negative regulation of endothelial cell-matrix adhesion via fibronectin / bronchiole development / positive regulation of epithelial cell proliferation involved in wound healing / elastin catabolic process / regulation of defense response to virus by host / positive regulation of type I interferon-mediated signaling pathway / wound healing, spreading of epidermal cells / negative regulation of type I interferon-mediated signaling pathway / lung alveolus development / response to amyloid-beta / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / positive regulation of interferon-alpha production / core promoter sequence-specific DNA binding / collagen binding / Degradation of the extracellular matrix / extracellular matrix organization / extracellular matrix / cellular response to virus / metalloendopeptidase activity / protein import into nucleus / endopeptidase activity / sequence-specific DNA binding / serine-type endopeptidase activity / calcium ion binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / proteolysis / extracellular space / zinc ion binding / extracellular region / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.485 Å | ||||||
Authors | Ciccone, L. / Tepshi, L. / Nuti, E. / Rossello, A. / Stura, E.A. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Development of Thioaryl-Based Matrix Metalloproteinase-12 Inhibitors with Alternative Zinc-Binding Groups: Synthesis, Potentiometric, NMR, and Crystallographic Studies. Authors: Nuti, E. / Cuffaro, D. / Bernardini, E. / Camodeca, C. / Panelli, L. / Chaves, S. / Ciccone, L. / Tepshi, L. / Vera, L. / Orlandini, E. / Nencetti, S. / Stura, E.A. / Santos, M.A. / Dive, V. / Rossello, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6ela.cif.gz | 316.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ela.ent.gz | 256 KB | Display | PDB format |
PDBx/mmJSON format | 6ela.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ela_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6ela_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6ela_validation.xml.gz | 35.7 KB | Display | |
Data in CIF | 6ela_validation.cif.gz | 53.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/el/6ela ftp://data.pdbj.org/pub/pdb/validation_reports/el/6ela | HTTPS FTP |
-Related structure data
Related structure data | 6eknC 6enmC 6eoxC 6esmC 5i4oS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 17557.568 Da / Num. of mol.: 4 / Mutation: F171D, K241A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Gene: MMP12, HME / Production host: Escherichia coli (E. coli) / References: UniProt: P39900, macrophage elastase |
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-Non-polymers , 6 types, 893 molecules
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-CA / #4: Chemical | ChemComp-B9Z / ( #5: Chemical | ChemComp-DIO / #6: Chemical | ChemComp-EDO / | #7: 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: 2.2 Å3/Da / Density % sol: 44.13 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: protein solution: hMMP12 at 314 micro-M + 10 milli-M acetohydroxamate + 1 milli-M BE4, 10% DMSO precipitant: 38% PEG 4K, 0.16 M imidazole piperidine,15% Dioxane, pH 8.5. Cryoprotectant: 40% ...Details: protein solution: hMMP12 at 314 micro-M + 10 milli-M acetohydroxamate + 1 milli-M BE4, 10% DMSO precipitant: 38% PEG 4K, 0.16 M imidazole piperidine,15% Dioxane, pH 8.5. Cryoprotectant: 40% CM15 (12.5 % diethylene glycol + 12.5 % ethylene glycol + 12.5 % MPD + 12.5 % glycerol + 12.5 % 1,2-propanediol + 12.5 % 1,4-dioxane + 12.5 mM NDSB 201), 25% PEG 6K, 100 milli-M TRIS HCl, pH 7.0 PH range: 7-8.5 / Temp details: cooled incubator |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: cryostream |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.976254 Å |
Detector | Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 30, 2016 / Details: microfocus |
Radiation | Monochromator: mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976254 Å / Relative weight: 1 |
Reflection | Resolution: 1.48→43.44 Å / Num. obs: 100074 / % possible obs: 99.4 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.67 % / CC1/2: 0.997 / Rrim(I) all: 0.137 / Rsym value: 0.127 / Net I/σ(I): 7.85 |
Reflection shell | Resolution: 1.48→1.57 Å / Redundancy: 6.51 % / Mean I/σ(I) obs: 1.68 / Num. unique obs: 15656 / CC1/2: 0.874 / Rrim(I) all: 0.85 / Rsym value: 0.78 / % possible all: 96.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5I4O Resolution: 1.485→38.041 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.01 / Phase error: 26.58 / 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: 1.485→38.041 Å
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Refine LS restraints |
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LS refinement shell |
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