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Yorodumi- PDB-2a8h: Crystal structure of catalytic domain of TACE with Thiomorpholine... -
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-Basic information
Entry | Database: PDB / ID: 2a8h | ||||||
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Title | Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor | ||||||
Components | ADAM 17 | ||||||
Keywords | HYDROLASE / TACE/ADAM-17 / TACE-inhibitor complex / Zn-endopeptidase | ||||||
Function / homology | Function and homology information ADAM 17 endopeptidase / regulation of mast cell apoptotic process / metalloendopeptidase activity involved in amyloid precursor protein catabolic process / cellular response to high density lipoprotein particle stimulus / positive regulation of epidermal growth factor-activated receptor activity / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / Notch receptor processing / interleukin-6 receptor binding / tumor necrosis factor binding / positive regulation of T cell chemotaxis ...ADAM 17 endopeptidase / regulation of mast cell apoptotic process / metalloendopeptidase activity involved in amyloid precursor protein catabolic process / cellular response to high density lipoprotein particle stimulus / positive regulation of epidermal growth factor-activated receptor activity / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / Notch receptor processing / interleukin-6 receptor binding / tumor necrosis factor binding / positive regulation of T cell chemotaxis / TNF signaling / positive regulation of leukocyte chemotaxis / germinal center formation / Regulated proteolysis of p75NTR / Release of Hh-Np from the secreting cell / commissural neuron axon guidance / positive regulation of tumor necrosis factor-mediated signaling pathway / neutrophil mediated immunity / Notch binding / wound healing, spreading of epidermal cells / negative regulation of cold-induced thermogenesis / CD163 mediating an anti-inflammatory response / positive regulation of vascular endothelial cell proliferation / cell adhesion mediated by integrin / positive regulation of epidermal growth factor receptor signaling pathway / Signaling by EGFR / amyloid precursor protein catabolic process / membrane protein ectodomain proteolysis / Collagen degradation / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of blood vessel endothelial cell migration / Nuclear signaling by ERBB4 / Growth hormone receptor signaling / positive regulation of chemokine production / Notch signaling pathway / spleen development / Constitutive Signaling by NOTCH1 HD Domain Mutants / Activated NOTCH1 Transmits Signal to the Nucleus / B cell differentiation / PDZ domain binding / cell motility / negative regulation of transforming growth factor beta receptor signaling pathway / metalloendopeptidase activity / protein processing / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / SH3 domain binding / metallopeptidase activity / actin cytoskeleton / integrin binding / T cell differentiation in thymus / peptidase activity / positive regulation of cell growth / endopeptidase activity / response to lipopolysaccharide / response to hypoxia / cell adhesion / positive regulation of cell migration / defense response to Gram-positive bacterium / response to xenobiotic stimulus / membrane raft / apical plasma membrane / endoplasmic reticulum lumen / Golgi membrane / positive regulation of cell population proliferation / cell surface / proteolysis / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Levin, J.I. / Chen, J.M. / Laakso, L.M. / Du, M. / Schmid, J. / Xu, W. / Cummons, T. / Xu, J. / Jin, G. / Barone, D. / Skotnicki, J.S. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2006 Title: Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Authors: Levin, J.I. / Chen, J.M. / Laakso, L.M. / Du, M. / Schmid, J. / Xu, W. / Cummons, T. / Xu, J. / Jin, G. / Barone, D. / Skotnicki, J.S. #1: Journal: To be Published Title: Acetylenic TACE Inhibitors. Part 2. SAR of 6-Membered Cyclic Sulfonamide Hydroxamates. Authors: Cowling, R. / Barone, D. / Black, R.A. / Skotnicki, J.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2a8h.cif.gz | 120.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2a8h.ent.gz | 92.8 KB | Display | PDB format |
PDBx/mmJSON format | 2a8h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a8/2a8h ftp://data.pdbj.org/pub/pdb/validation_reports/a8/2a8h | HTTPS FTP |
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-Related structure data
Related structure data | 1bkcS 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 30710.342 Da / Num. of mol.: 2 / Fragment: catalytic domain / Mutation: S266A, N452Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ADAM17, CSVP, TACE / Production host: Escherichia coli (E. coli) / References: UniProt: P78536, ADAM 17 endopeptidase #2: Chemical | #3: Chemical | #4: 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: 42.5 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 5.4 Details: PEG 4000, isopropanol, NaCitrate, pH 5.4, VAPOR DIFFUSION, SITTING DROP, temperature 292K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Jan 10, 2000 |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→20 Å / Num. all: 31848 / Num. obs: 31529 / % possible obs: 99.14 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Rmerge(I) obs: 0.057 |
Reflection shell | Resolution: 2.299→2.358 Å / % possible all: 96.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1BKC Resolution: 2.3→20 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.887 / SU B: 5.111 / SU ML: 0.129 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.385 / ESU R Free: 0.275 / 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: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.205 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.299→2.358 Å / Total num. of bins used: 20
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