+Open data
-Basic information
Entry | Database: PDB / ID: 6ekn | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of MMP12 in complex with inhibitor BE7. | ||||||
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 / 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: 1.2 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6ekn.cif.gz | 93.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6ekn.ent.gz | 69.3 KB | Display | PDB format |
PDBx/mmJSON format | 6ekn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ekn_validation.pdf.gz | 715.2 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6ekn_full_validation.pdf.gz | 717.5 KB | Display | |
Data in XML | 6ekn_validation.xml.gz | 10.9 KB | Display | |
Data in CIF | 6ekn_validation.cif.gz | 15.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ek/6ekn ftp://data.pdbj.org/pub/pdb/validation_reports/ek/6ekn | HTTPS FTP |
-Related structure data
Related structure data | 6elaC 6enmC 6eoxC 6esmC 4i03S S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
Unit cell |
| ||||||||||||
Components on special symmetry positions |
|
-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 17615.670 Da / Num. of mol.: 1 / Mutation: F171D Source method: isolated from a genetically manipulated source Details: metalloprotease / Source: (gene. exp.) Homo sapiens (human) / Cell: macrophage / Gene: MMP12, HME / Production host: Escherichia coli (E. coli) / References: UniProt: P39900, macrophage elastase |
---|
-Non-polymers , 5 types, 153 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-B9N / ( | #5: Chemical | ChemComp-EDO / | #6: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.16 Å3/Da / Density % sol: 43.15 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 10 Details: Protein: 1 micro-L MMP12 at 290 micro-M with 10 milli-M acetohydroxamate + 0.1 Micro-L BE6 from 10 milii-M in 100% DMSO Precipitant: 17% PEG 20K, 250 milli-M NaCl, 100 milii-M TRIS HCl, pH ...Details: Protein: 1 micro-L MMP12 at 290 micro-M with 10 milli-M acetohydroxamate + 0.1 Micro-L BE6 from 10 milii-M in 100% DMSO Precipitant: 17% PEG 20K, 250 milli-M NaCl, 100 milii-M TRIS HCl, pH 10.0. cryoprotectant: 40% (25 % di-ethylene glycol + 25 % glycerol + 25 % 1,2-propanediol) 10 % PEG 10K, 200 milli-M NaCl, 100 milli-M AAB (Na acetate,N-(2-Acetamido)iminodiacetic acid (ADA), Bicine) 10% acid/90% basic Temp details: cooled incubator |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: cryostream |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.980035 Å |
Detector | Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Nov 23, 2016 / Details: microfocus |
Radiation | Monochromator: mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.980035 Å / Relative weight: 1 |
Reflection | Resolution: 1.2→36.74 Å / Num. obs: 46976 / % possible obs: 99.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.61 % / CC1/2: 0.998 / Rrim(I) all: 0.096 / Rsym value: 0.088 / Net I/σ(I): 10.21 |
Reflection shell | Resolution: 1.2→1.23 Å / Redundancy: 6.18 % / Mean I/σ(I) obs: 0.98 / Num. unique obs: 3280 / CC1/2: 0.32 / Rrim(I) all: 1.8 / Rsym value: 1.65 / % possible all: 94.7 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4I03 Resolution: 1.2→36.74 Å / Cor.coef. Fo:Fc: 0.985 / Cor.coef. Fo:Fc free: 0.979 / SU B: 1.786 / SU ML: 0.031 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.04 / ESU R Free: 0.04 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.711 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 1.2→36.74 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|