[English] 日本語
Yorodumi- PDB-4kfn: Structure-Based Discovery of Novel Amide-Containing Nicotinamide ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4kfn | ||||||
---|---|---|---|---|---|---|---|
Title | Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors | ||||||
Components | Nicotinamide phosphoribosyltransferase | ||||||
Keywords | Transferase/Transferase Inhibitor / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / NAD biosynthesis via nicotinamide riboside salvage pathway / Nicotinamide salvaging / NAD biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian gene expression / cytokine activity / circadian regulation of gene expression ...nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / NAD biosynthesis via nicotinamide riboside salvage pathway / Nicotinamide salvaging / NAD biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian gene expression / cytokine activity / circadian regulation of gene expression / cell junction / cell-cell signaling / nuclear speck / positive regulation of cell population proliferation / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular exosome / identical protein binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Zheng, X. / Bauer, P. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y. / Kley, N. / Lin, J. ...Zheng, X. / Bauer, P. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y. / Kley, N. / Lin, J. / Reynolds, D.J. / Sharma, G. / Smith, C.C. / Wang, Z. / Dragovich, P.S. / Gunzner-Toste, J. / Liederer, B.M. / Ly, J. / O'Brien, T. / Oh, A. / Wang, L. / Wang, W. / Xiao, Y. / Zak, M. / Zhao, G. / Yuen, P. / Bair, K.W. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (nampt) inhibitors. Authors: Zheng, X. / Bauer, P. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y.C. / Kley, N. / Lin, J. / Reynolds, D.J. / Sharma, G. / Smith, C.C. / Wang, Z. ...Authors: Zheng, X. / Bauer, P. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y.C. / Kley, N. / Lin, J. / Reynolds, D.J. / Sharma, G. / Smith, C.C. / Wang, Z. / Dragovich, P.S. / Oh, A. / Wang, W. / Zak, M. / Gunzner-Toste, J. / Zhao, G. / Yuen, P.W. / Bair, K.W. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4kfn.cif.gz | 414.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4kfn.ent.gz | 336.6 KB | Display | PDB format |
PDBx/mmJSON format | 4kfn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kf/4kfn ftp://data.pdbj.org/pub/pdb/validation_reports/kf/4kfn | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 56942.375 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NAMPT, PBEF, PBEF1 / Production host: Escherichia coli (E. coli) References: UniProt: P43490, nicotinamide phosphoribosyltransferase #2: Chemical | #3: Chemical | ChemComp-PO4 / #4: Chemical | ChemComp-EDO / #5: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.33 Å3/Da / Density % sol: 47.28 % |
---|---|
Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 8.6 Details: 0.2uL + 0.2uL drops containing 6mg/mL Nampt, 0.1M Sodium phosphate, 25-29% polyethylene glycol 3350, 0.2M NaCl, 1mM compound, pH 8.6, VAPOR DIFFUSION, HANGING DROP, temperature 292K |
-Data collection
Diffraction | Mean temperature: 93 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.984 |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 21, 2012 |
Radiation | Monochromator: Double-crystal, Si(111) liquid N2 cooled / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.984 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→50 Å / Num. all: 138245 / Num. obs: 135066 / % possible obs: 97.7 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 |
Reflection shell | Resolution: 1.6→1.66 Å / % possible all: 96.1 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→42.285 Å / SU ML: 0.18 / σ(F): 1.34 / Phase error: 18.66 / Stereochemistry target values: ML
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 41.474 Å2 / ksol: 0.366 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.6→42.285 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: 13.3585 Å / Origin y: 1.1671 Å / Origin z: 22.5978 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group | Selection details: ALL |