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Yorodumi- PDB-5upf: Crystal structure of human NAMPT with isoindoline urea inhibitor ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5upf | ||||||
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Title | Crystal structure of human NAMPT with isoindoline urea inhibitor compound 53 | ||||||
Components | Nicotinamide phosphoribosyltransferase | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / NAMPT 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: 1.69 Å | ||||||
Authors | Longenecker, K.L. / Raich, D. / Korepanova, A.V. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2017 Title: SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT). Authors: Curtin, M.L. / Heyman, H.R. / Clark, R.F. / Sorensen, B.K. / Doherty, G.A. / Hansen, T.M. / Frey, R.R. / Sarris, K.A. / Aguirre, A.L. / Shrestha, A. / Tu, N. / Woller, K. / Pliushchev, M.A. ...Authors: Curtin, M.L. / Heyman, H.R. / Clark, R.F. / Sorensen, B.K. / Doherty, G.A. / Hansen, T.M. / Frey, R.R. / Sarris, K.A. / Aguirre, A.L. / Shrestha, A. / Tu, N. / Woller, K. / Pliushchev, M.A. / Sweis, R.F. / Cheng, M. / Wilsbacher, J.L. / Kovar, P.J. / Guo, J. / Cheng, D. / Longenecker, K.L. / Raich, D. / Korepanova, A.V. / Soni, N.B. / Algire, M.A. / Richardson, P.L. / Marin, V.L. / Badagnani, I. / Vasudevan, A. / Buchanan, F.G. / Maag, D. / Chiang, G.G. / Tse, C. / Michaelides, M.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5upf.cif.gz | 215.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5upf.ent.gz | 168.4 KB | Display | PDB format |
PDBx/mmJSON format | 5upf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5upf_validation.pdf.gz | 908.3 KB | Display | wwPDB validaton report |
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Full document | 5upf_full_validation.pdf.gz | 913.6 KB | Display | |
Data in XML | 5upf_validation.xml.gz | 40.3 KB | Display | |
Data in CIF | 5upf_validation.cif.gz | 60.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/up/5upf ftp://data.pdbj.org/pub/pdb/validation_reports/up/5upf | HTTPS FTP |
-Related structure data
Related structure data | 5upeC 2gvjS 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: 56591.898 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NAMPT, PBEF, PBEF1 / Cell line (production host): HEK 293-6E / Production host: Mammalia (mammals) References: UniProt: P43490, nicotinamide phosphoribosyltransferase #2: Chemical | #3: 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: 2.38 Å3/Da / Density % sol: 48.33 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 25% PEG 3350, 0.2 M ammonium sulfate, and 0.1 M HEPES, pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.69→82.74 Å / Num. obs: 109884 / % possible obs: 92.8 % / Redundancy: 3.1 % / Biso Wilson estimate: 21.5 Å2 / CC1/2: 0.982 / Rmerge(I) obs: 0.111 / Rpim(I) all: 0.072 / Rrim(I) all: 0.132 / Rsym value: 0.111 / Net I/σ(I): 9.7 / Num. measured all: 339858 |
Reflection shell | Resolution: 1.69→1.695 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.655 / Mean I/σ(I) obs: 2.1 / CC1/2: 0.789 / Rpim(I) all: 0.437 / Rrim(I) all: 0.749 / Rsym value: 0.655 / % possible all: 75.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2GVJ Resolution: 1.69→24.74 Å / Cor.coef. Fo:Fc: 0.924 / Cor.coef. Fo:Fc free: 0.907 / SU R Cruickshank DPI: 0.122 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.125 / SU Rfree Blow DPI: 0.115 / SU Rfree Cruickshank DPI: 0.115
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Displacement parameters | Biso max: 103.71 Å2 / Biso mean: 22.92 Å2 / Biso min: 5.77 Å2
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Refine analyze | Luzzati coordinate error obs: 0.26 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.69→24.74 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.69→1.73 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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