[English] 日本語
Yorodumi- PDB-6w0y: Structure of KHK in complex with compound 6 (2-[(1~{R},5~{S})-3-[... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6w0y | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of KHK in complex with compound 6 (2-[(1~{R},5~{S})-3-[5-cyano-6-[(2~{S},3~{R})-2-methyl-3-oxidanyl-azetidin-1-yl]-4-(trifluoromethyl)pyridin-2-yl]-3-azabicyclo[3.1.0]hexan-6-yl]ethanoic acid) | ||||||
Components | KetohexokinaseHepatic fructokinase | ||||||
Keywords | TRANSFERASE / Ketohexokinase | ||||||
Function / homology | Function and homology information Essential fructosuria / ketohexokinase / ketohexokinase activity / Fructose catabolism / regulation of glycogen metabolic process / response to sucrose / response to fructose / fructose metabolic process / response to zinc ion / response to glucose ...Essential fructosuria / ketohexokinase / ketohexokinase activity / Fructose catabolism / regulation of glycogen metabolic process / response to sucrose / response to fructose / fructose metabolic process / response to zinc ion / response to glucose / response to insulin / extracellular exosome / ATP binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.54 Å | ||||||
Authors | Jasti, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose. Authors: Futatsugi, K. / Smith, A.C. / Tu, M. / Raymer, B. / Ahn, K. / Coffey, S.B. / Dowling, M.S. / Fernando, D.P. / Gutierrez, J.A. / Huard, K. / Jasti, J. / Kalgutkar, A.S. / Knafels, J.D. / ...Authors: Futatsugi, K. / Smith, A.C. / Tu, M. / Raymer, B. / Ahn, K. / Coffey, S.B. / Dowling, M.S. / Fernando, D.P. / Gutierrez, J.A. / Huard, K. / Jasti, J. / Kalgutkar, A.S. / Knafels, J.D. / Pandit, J. / Parris, K.D. / Perez, S. / Pfefferkorn, J.A. / Price, D.A. / Ryder, T. / Shavnya, A. / Stock, I.A. / Tsai, A.S. / Tesz, G.J. / Thuma, B.A. / Weng, Y. / Wisniewska, H.M. / Xing, G. / Zhou, J. / Magee, T.V. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6w0y.cif.gz | 252.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6w0y.ent.gz | 203 KB | Display | PDB format |
PDBx/mmJSON format | 6w0y.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w0/6w0y ftp://data.pdbj.org/pub/pdb/validation_reports/w0/6w0y | HTTPS FTP |
---|
-Related structure data
Related structure data | 6w0nC 6w0wC 6w0xC 6w0zC 5wbmS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 34076.586 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KHK / Production host: Escherichia coli (E. coli) / References: UniProt: P50053, ketohexokinase #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.46 Å3/Da / Density % sol: 64.42 % |
---|---|
Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop Details: 17-20% PEG8000, 100 mM sodium citrate, pH 4.4-4.7, 0.2 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 24, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.54→83.56 Å / Num. obs: 31606 / % possible obs: 99.2 % / Redundancy: 6.1 % / CC1/2: 0.998 / Net I/σ(I): 18 |
Reflection shell | Resolution: 2.54→3.11 Å / Num. unique obs: 14038 / CC1/2: 0.973 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 5WBM Resolution: 2.54→44.57 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.937 / SU R Cruickshank DPI: 0.292 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.308 / SU Rfree Blow DPI: 0.207 / SU Rfree Cruickshank DPI: 0.205
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 191.2 Å2 / Biso mean: 76.51 Å2 / Biso min: 36.8 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.29 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.54→44.57 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.54→2.56 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|