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Yorodumi- PDB-4lww: Discovery of Potent and Efficacious Cyanoguanidine-containing Nic... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4lww | ||||||
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Title | Discovery of Potent and Efficacious Cyanoguanidine-containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors | ||||||
Components | Nicotinamide phosphoribosyltransferase | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Transferase / 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: 1.641 Å | ||||||
Authors | Zheng, X. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y. / Kley, N. / Lin, J. / Reynoids, D.J. ...Zheng, X. / Baumeister, T. / Buckmelter, A.J. / Caligiuri, M. / Clodfelter, K.H. / Han, B. / Ho, Y. / Kley, N. / Lin, J. / Reynoids, D.J. / Sharma, G. / Smith, C.C. / Wang, Z. / Dragovich, P.S. / Oh, A. / Wang, W. / Zak, M. / Wang, L. / Yuen, P. / Bair, K.W. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2014 Title: Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors. Authors: Zheng, X. / 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, ...Authors: Zheng, X. / 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. / Wang, Y. / Yuen, P.W. / Bair, K.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4lww.cif.gz | 429 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4lww.ent.gz | 349.6 KB | Display | PDB format |
PDBx/mmJSON format | 4lww.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lw/4lww ftp://data.pdbj.org/pub/pdb/validation_reports/lw/4lww | HTTPS FTP |
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-Related structure data
Related structure data | 4ltsC 3dhfS C: citing same article (ref.) 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
#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 / | |
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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: 2.33 Å3/Da / Density % sol: 47.14 % |
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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 |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.97949 Å |
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: May 30, 2013 |
Radiation | Monochromator: Double Crystal Monochromator (ACCEL DCM) with an indirectly cryo-cooled first crystal and sagittally focusing second crystal Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 |
Reflection | Resolution: 1.64→50 Å / Num. all: 126639 / Num. obs: 125879 / % possible obs: 99.4 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Biso Wilson estimate: 15.97 Å2 |
Reflection shell | Resolution: 1.64→1.7 Å / % possible all: 98.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3DHF Resolution: 1.641→46.254 Å / SU ML: 0.16 / σ(F): 1.34 / Phase error: 18.54 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.641→46.254 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 13.4314 Å / Origin y: 1.1559 Å / Origin z: 22.6843 Å
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Refinement TLS group | Selection details: chain A or chain B |