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Yorodumi- PDB-5i43: Crystal structure of the catalytic domain of MMP-12 in complex wi... -
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-Basic information
Entry | Database: PDB / ID: 5i43 | ||||||
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Title | Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate chelator water-soluble inhibitor (DC32). | ||||||
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: 1.95 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 | 5i43.cif.gz | 169.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5i43.ent.gz | 133.2 KB | Display | PDB format |
PDBx/mmJSON format | 5i43.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5i43_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 5i43_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 5i43_validation.xml.gz | 39 KB | Display | |
Data in CIF | 5i43_validation.cif.gz | 53.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i4/5i43 ftp://data.pdbj.org/pub/pdb/validation_reports/i4/5i43 | HTTPS FTP |
-Related structure data
Related structure data | 5i0lC 5i12C 5i2zC 5i3mSC 5i4oC S: Starting model for refinement C: citing same article (ref.) |
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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: 17614.684 Da / Num. of mol.: 4 / Mutation: F171D, E219Q Source method: isolated from a genetically manipulated source Details: Fragment: catalitic subunit (UNP RESIDUES 106-263) / 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 |
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-Non-polymers , 7 types, 650 molecules
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-CA / #4: Chemical | ChemComp-67M / ( Mass: 801.860 Da / Num. of mol.: 4 / Mutation: F171D, E219Q Source method: isolated from a genetically manipulated source Formula: C37H47N5O13S / Details: Fragment: catalitic subunit (UNP RESIDUES 106-263) / Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star / References: macrophage elastase #5: Chemical | ChemComp-EDO / #6: Chemical | #7: Chemical | ChemComp-PGO / #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: 2.2 Å3/Da / Density % sol: 44.2 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Protein-ligand: hMMP12 F171D E219Q 465 micro-M in 0.020 M Tris-HCl, 3 milli-M CaCl2, 0.2 M NaCl, 0.02 M acetohydroxamic acid, 10% DMSO, pH 7.5, 0.5 milli-M inhibitor (DC31). Precipitant: 40% ...Details: Protein-ligand: hMMP12 F171D E219Q 465 micro-M in 0.020 M Tris-HCl, 3 milli-M CaCl2, 0.2 M NaCl, 0.02 M acetohydroxamic acid, 10% DMSO, pH 7.5, 0.5 milli-M inhibitor (DC31). Precipitant: 40% PEG4K, 9% dioxane, 0.18 M imidazole piperidine, pH 8.5. Cryoprotectant: 40% cryomix SM2:(12.5 % ethylene glycol + 12.5 % glycerol + 12.5 % 1,2-propanediol + 25 % DMSO + 37.5 % 1,4-dioxane), 22.5% MPEG 4K, 5% dioxane, 100 mM imidazole piperidine pH 8.5. PH range: 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 1 / Wavelength: 0.97857 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 8, 2015 / Details: mirrors |
Radiation | Monochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97857 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→44.56 Å / Num. obs: 45366 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 5.97 % / Biso Wilson estimate: 26.387 Å2 / CC1/2: 0.993 / Rmerge(I) obs: 0.172 / Rsym value: 0.167 / Net I/av σ(I): 12.744 / Net I/σ(I): 7.24 |
Reflection shell | Resolution: 1.95→2 Å / Redundancy: 3.96 % / Rmerge(I) obs: 0.716 / Mean I/σ(I) obs: 2.02 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5I3M Resolution: 1.95→44.56 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.938 / SU B: 4.535 / SU ML: 0.127 / Cross valid method: THROUGHOUT / ESU R: 0.224 / ESU R Free: 0.173 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 27.062 Å2
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Refinement step | Cycle: LAST / Resolution: 1.95→44.56 Å
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Refine LS restraints |
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