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Yorodumi- PDB-2hu6: Crystal structure of human MMP-12 in complex with acetohydroxamic... -
+Open data
-Basic information
Entry | Database: PDB / ID: 2hu6 | ||||||
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Title | Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor | ||||||
Components | Macrophage metalloelastase | ||||||
Keywords | HYDROLASE / MMP-12 / matrix metalloproteinase / macrophage metalloelastase / inhibitor / hydroxamic acid / drug design | ||||||
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 / lung alveolus development / negative regulation of type I interferon-mediated signaling pathway ...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 / lung alveolus development / negative regulation of type I interferon-mediated signaling pathway / 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 / extracellular matrix organization / 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: 1.32 Å | ||||||
Authors | Mannino, C. / Nievo, M. / Machetti, F. / Papakyriakou, A. / Calderone, V. / Fragai, M. / Guarna, A. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2006 Title: Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors. Authors: Mannino, C. / Nievo, M. / Machetti, F. / Papakyriakou, A. / Calderone, V. / Fragai, M. / Guarna, A. #1: Journal: Proc.Natl.Acad.Sci.USA / Year: 2005 Title: Conformational variability of matrix metalloproteinases: beyond a single 3D structure. Authors: Bertini, I. / Calderone, V. / Cosenza, M. / Fragai, M. / Lee, Y.-M. / Luchinat, C. / Mangani, S. / Turano, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2hu6.cif.gz | 89.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2hu6.ent.gz | 65.2 KB | Display | PDB format |
PDBx/mmJSON format | 2hu6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2hu6_validation.pdf.gz | 775.8 KB | Display | wwPDB validaton report |
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Full document | 2hu6_full_validation.pdf.gz | 776.4 KB | Display | |
Data in XML | 2hu6_validation.xml.gz | 11 KB | Display | |
Data in CIF | 2hu6_validation.cif.gz | 16.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hu/2hu6 ftp://data.pdbj.org/pub/pdb/validation_reports/hu/2hu6 | HTTPS FTP |
-Related structure data
Related structure data | 1y93S S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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Details | The protein is monomeric in vivo and there is one molecule in the asymmetric unit. |
-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 17615.670 Da / Num. of mol.: 1 / Fragment: Catalytic Domain (residues 106-263) / Mutation: F171D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MMP12, HME / Plasmid: pET21 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: P39900, macrophage elastase |
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-Non-polymers , 5 types, 263 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-37A / ( | #5: Chemical | ChemComp-HAE / | #6: 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: 2.15 Å3/Da / Density % sol: 42.72 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 0.1 M Tris-HCl, 30% PEG 6000, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: EMBL/DESY, HAMBURG / Beamline: BW7A / Wavelength: 0.9392 Å |
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Jul 26, 2005 Details: Fixed exit double crystal Si [111], horizontally focusing |
Radiation | Monochromator: Fixed exit double crystal Si [111], horizontally focusing Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9392 Å / Relative weight: 1 |
Reflection | Resolution: 1.32→49.08 Å / Num. all: 34648 / Num. obs: 34648 / % possible obs: 99.1 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.1 % / Biso Wilson estimate: 10.41 Å2 / Rmerge(I) obs: 0.053 / Rsym value: 0.053 / Net I/σ(I): 8.6 |
Reflection shell | Resolution: 1.32→1.39 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.282 / Mean I/σ(I) obs: 2.1 / Num. unique all: 4823 / Rsym value: 0.282 / % possible all: 95.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 1Y93 Resolution: 1.32→25.68 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.956 / SU B: 1.57 / SU ML: 0.03 / Isotropic thermal model: Anisotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.064 / ESU R Free: 0.055 / 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: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 13.577 Å2
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Refine analyze | Luzzati sigma a obs: 0.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.32→25.68 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.32→1.354 Å / Total num. of bins used: 20
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