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Yorodumi- PDB-5i4o: Crystal structure of the catalytic domain of MMP-12 in complex wi... -
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-Basic information
Entry | Database: PDB / ID: 5i4o | ||||||
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Title | Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate zinc-chelator water-soluble inhibitor (DC28). | ||||||
Components | Macrophage metalloelastase | ||||||
Keywords | HYDROLASE / Inhibitor / complex / glycoconjugate / metalloprotease | ||||||
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: 2.05 Å | ||||||
Authors | Stura, E.A. / Rosalia, L. / Cuffaro, D. / Tepshi, L. / Ciccone, L. / Rossello, A. | ||||||
Citation | Journal: Chemmedchem / Year: 2016 Title: Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. Authors: Nuti, E. / Cuffaro, D. / D'Andrea, F. / Rosalia, L. / Tepshi, L. / Fabbi, M. / Carbotti, G. / Ferrini, S. / Santamaria, S. / Camodeca, C. / Ciccone, L. / Orlandini, E. / Nencetti, S. / ...Authors: Nuti, E. / Cuffaro, D. / D'Andrea, F. / Rosalia, L. / Tepshi, L. / Fabbi, M. / Carbotti, G. / Ferrini, S. / Santamaria, S. / Camodeca, C. / Ciccone, L. / Orlandini, E. / Nencetti, S. / Stura, E.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 | 5i4o.cif.gz | 155.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5i4o.ent.gz | 121.6 KB | Display | PDB format |
PDBx/mmJSON format | 5i4o.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5i4o_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 5i4o_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 5i4o_validation.xml.gz | 33.9 KB | Display | |
Data in CIF | 5i4o_validation.cif.gz | 46.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i4/5i4o ftp://data.pdbj.org/pub/pdb/validation_reports/i4/5i4o | HTTPS FTP |
-Related structure data
Related structure data | 5i0lC 5i12C 5i2zC 5i3mC 5i43C 5iolS 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
#1: Protein | Mass: 17614.684 Da / Num. of mol.: 4 / Fragment: UNP residues 106-238 / Mutation: F171D, E219Q Source method: isolated from a genetically manipulated source Details: Catalytic domain of human macrophage elastase (MMP-12) Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Gene: MMP12, HME / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star / References: UniProt: P39900, macrophage elastase #2: Chemical | ChemComp-V28 / Mass: 617.671 Da / Num. of mol.: 4 / Mutation: F171D, E219Q Source method: isolated from a genetically manipulated source Formula: C28H35N5O9S Details: Catalytic domain of human macrophage elastase (MMP-12) Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star / 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: 2.22 Å3/Da / Density % sol: 44.54 % / Description: small thin plates |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Protein-ligand: 465 micro-M hMMP12 F171D E219Q, 0.020 M acetohydroxamic acid, 10% DMSO, 0.5 milli-M inhibitor (DC28). Precipitant: 40.5% PEG4K, 10% dioxane, 2% ethylene glycol, 0.18 M ...Details: Protein-ligand: 465 micro-M hMMP12 F171D E219Q, 0.020 M acetohydroxamic acid, 10% DMSO, 0.5 milli-M inhibitor (DC28). Precipitant: 40.5% PEG4K, 10% dioxane, 2% ethylene glycol, 0.18 M imidazole piperidine, pH 8.5. Cryoprotectant:40% cryomix CM12: (,25 % diethylene glycol + 12.5 % glycerol + 25 % 1,2-propanediol + 12.5 % 1,4-dioxane), 25% PEG 6K, 0.1 M TRIS HCl, pH 8.0. PH range: 8-8.5 / Temp details: cooled incubator |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: cryonozzle |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.9801 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 24, 2014 / Details: mirrors |
Radiation | Monochromator: Cryogenically cooled channel cut Si[111] crystal monochromator Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9801 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→44.56 Å / Num. obs: 45133 / % possible obs: 98.4 % / Observed criterion σ(I): -3 / Redundancy: 4.49 % / Biso Wilson estimate: 24.46 Å2 / Rmerge(I) obs: 0.23 / Rsym value: 0.21 / Net I/σ(I): 4.79 |
Reflection shell | Resolution: 1.95→2 Å / Redundancy: 4.25 % / Rmerge(I) obs: 0.985 / Mean I/σ(I) obs: 1.68 / % possible all: 86.8 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5IOL Resolution: 2.05→32.87 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.911 / SU B: 5.127 / SU ML: 0.138 / Cross valid method: THROUGHOUT / ESU R: 0.278 / ESU R Free: 0.204 / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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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: 30 Å2
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Refinement step | Cycle: LAST / Resolution: 2.05→32.87 Å
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Refine LS restraints |
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