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Yorodumi- PDB-6enm: Crystal structure of MMP12 in complex with hydroxamate inhibitor ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6enm | ||||||
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Title | Crystal structure of MMP12 in complex with hydroxamate inhibitor LP168. | ||||||
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 / positive regulation of interferon-alpha production / response to amyloid-beta / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / core promoter sequence-specific DNA binding / collagen binding / Degradation of the extracellular matrix / extracellular matrix organization / extracellular matrix / metalloendopeptidase activity / cellular response to virus / 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: 1.59 Å | ||||||
Authors | Vera, 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 | 6enm.cif.gz | 89.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6enm.ent.gz | 67.8 KB | Display | PDB format |
PDBx/mmJSON format | 6enm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/en/6enm ftp://data.pdbj.org/pub/pdb/validation_reports/en/6enm | HTTPS FTP |
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-Related structure data
Related structure data | 6eknC 6elaC 6eoxC 6esmC 4h76S 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 17615.670 Da / Num. of mol.: 2 / Mutation: F171D Source method: isolated from a genetically manipulated source Details: matrix metalloprotein 12 / Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Gene: MMP12, HME / Production host: Escherichia coli (E. coli) / References: UniProt: P39900, macrophage elastase #2: Chemical | Mass: 397.444 Da / Num. of mol.: 2 / Mutation: F171D Source method: isolated from a genetically manipulated source Formula: C21H19NO5S / Details: matrix metalloprotein 12 / Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Production host: Escherichia coli (E. coli) / References: macrophage elastase #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-CA / #5: 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 Å3/Da / Density % sol: 38.53 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Drops: 1 micro-L hMMP12 at 927 micro-M + 10 mM acetohydroxamic acid, LP168 at 1 milli-M and 1 micro-L precipitant. Precipitant: 17% PEG 20K, 0.2 M imidazole malate, pH 8.5, 0.250 M NaCl ...Details: Drops: 1 micro-L hMMP12 at 927 micro-M + 10 mM acetohydroxamic acid, LP168 at 1 milli-M and 1 micro-L precipitant. Precipitant: 17% PEG 20K, 0.2 M imidazole malate, pH 8.5, 0.250 M NaCl cryoprotectant: 27% PEG8K, 15% MPEG550, 10% glycerol, 90mM Tris-HCl, pH 8.0 PH range: 8.0-8.5 / 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 1 / Wavelength: 0.9184 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 20, 2010 / Details: mirrors |
Radiation | Monochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9184 Å / Relative weight: 1 |
Reflection | Resolution: 1.59→47.91 Å / Num. obs: 38794 / % possible obs: 99.7 % / Observed criterion σ(I): -3 / Redundancy: 7.93 % / Rsym value: 0.123 / Net I/σ(I): 12.1 |
Reflection shell | Resolution: 1.59→1.68 Å / Redundancy: 8.11 % / Mean I/σ(I) obs: 2.9 / Rsym value: 0.85 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4H76 Resolution: 1.59→47.91 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.96 / SU B: 1.884 / SU ML: 0.065 / Cross valid method: THROUGHOUT / ESU R: 0.098 / ESU R Free: 0.093 / Details: HYDROGENS HAVE BEEN ADDED IN THE 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 18.65 Å2
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Refinement step | Cycle: LAST / Resolution: 1.59→47.91 Å
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