[English] 日本語
Yorodumi- PDB-7t78: CRYSTAL STRUCTURE OF GLUCOKINASE (HEXOKINASE 4) COMPLEXED WITH LI... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7t78 | ||||||
---|---|---|---|---|---|---|---|
Title | CRYSTAL STRUCTURE OF GLUCOKINASE (HEXOKINASE 4) COMPLEXED WITH LIGAND DIETHYL ({2-[3-(4-METHANESULFONYLPHENO XY)-5-{[(2S)-1-METHOXYPROPAN-2-YL]OXY}BENZAMIDO]-1,3-THIAZ OL-4-YL}METHYL)PHOSPHONATE | ||||||
Components | Isoform 2 of Hexokinase-4 | ||||||
Keywords | TRANSFERASE | ||||||
Function / homology | Function and homology information Defective GCK causes maturity-onset diabetes of the young 2 (MODY2) / mannokinase activity / glucose sensor activity / regulation of potassium ion transport / hexokinase / fructokinase activity / carbohydrate phosphorylation / glucokinase activity / glucose catabolic process / glucose 6-phosphate metabolic process ...Defective GCK causes maturity-onset diabetes of the young 2 (MODY2) / mannokinase activity / glucose sensor activity / regulation of potassium ion transport / hexokinase / fructokinase activity / carbohydrate phosphorylation / glucokinase activity / glucose catabolic process / glucose 6-phosphate metabolic process / Regulation of Glucokinase by Glucokinase Regulatory Protein / Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) / NADP metabolic process / glucose binding / cellular response to leptin stimulus / calcium ion import / canonical glycolysis / Glycolysis / regulation of glycolytic process / intracellular glucose homeostasis / Regulation of gene expression in beta cells / regulation of insulin secretion / positive regulation of glycogen biosynthetic process / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / response to glucose / glycolytic process / positive regulation of insulin secretion / cellular response to insulin stimulus / glucose metabolic process / glucose homeostasis / mitochondrion / nucleoplasm / ATP binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.4 Å | ||||||
Authors | Muckelbauer, J.K. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: J.Med.Chem. / Year: 2022 Title: Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1 H -pyrazol-1-yl)methyl)phosphonate (BMS-820132). Authors: Shi, Y. / Wang, Y. / Meng, W. / Brigance, R.P. / Ryono, D.E. / Bolton, S. / Zhang, H. / Chen, S. / Smirk, R. / Tao, S. / Tino, J.A. / Williams, K.N. / Sulsky, R. / Nielsen, L. / Ellsworth, B. ...Authors: Shi, Y. / Wang, Y. / Meng, W. / Brigance, R.P. / Ryono, D.E. / Bolton, S. / Zhang, H. / Chen, S. / Smirk, R. / Tao, S. / Tino, J.A. / Williams, K.N. / Sulsky, R. / Nielsen, L. / Ellsworth, B. / Wong, M.K.Y. / Sun, J.H. / Leith, L.W. / Sun, D. / Wu, D.R. / Gupta, A. / Rampulla, R. / Mathur, A. / Chen, B.C. / Wang, A. / Fuentes-Catanio, H.G. / Kunselman, L. / Cap, M. / Zalaznick, J. / Ma, X. / Liu, H. / Taylor, J.R. / Zebo, R. / Jones, B. / Kalinowski, S. / Swartz, J. / Staal, A. / O'Malley, K. / Kopcho, L. / Muckelbauer, J.K. / Krystek Jr., S.R. / Spronk, S.A. / Marcinkeviciene, J. / Everlof, G. / Chen, X.Q. / Xu, C. / Li, Y.X. / Langish, R.A. / Yang, Y. / Wang, Q. / Behnia, K. / Fura, A. / Janovitz, E.B. / Pannacciulli, N. / Griffen, S. / Zinker, B.A. / Krupinski, J. / Kirby, M. / Whaley, J. / Zahler, R. / Barrish, J.C. / Robl, J.A. / Cheng, P.T.W. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7t78.cif.gz | 187.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7t78.ent.gz | 146 KB | Display | PDB format |
PDBx/mmJSON format | 7t78.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t7/7t78 ftp://data.pdbj.org/pub/pdb/validation_reports/t7/7t78 | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
-Protein / Sugars , 2 types, 4 molecules AB
#1: Protein | Mass: 52199.309 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GCK / Production host: Escherichia coli (E. coli) / References: UniProt: P35557, hexokinase #2: Sugar | |
---|
-Non-polymers , 4 types, 191 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-EDO / | #6: Water | ChemComp-HOH / | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.56 Å3/Da / Density % sol: 51.93 % |
---|---|
Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / Details: PEG 600, Hepes pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.97872 Å |
Detector | Type: RAYONIX MX-225 / Detector: CCD / Date: Jun 18, 2015 / Details: ??? |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97872 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→43.83 Å / Num. obs: 41325 / % possible obs: 99.9 % / Redundancy: 4.6 % / Biso Wilson estimate: 46.55 Å2 / CC1/2: 0.997 / Rrim(I) all: 0.094 / Χ2: 0.997 / Net I/σ(I): 15.4 |
Reflection shell | Resolution: 2.4→2.46 Å / Redundancy: 4.7 % / Rmerge(I) obs: 0.662 / Mean I/σ(I) obs: 3 / Num. unique obs: 484 / Rrim(I) all: 0.025 / Χ2: 0.786 / % possible all: 99.9 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.4→43.83 Å / Cor.coef. Fo:Fc: 0.9302 / Cor.coef. Fo:Fc free: 0.9019 / SU R Cruickshank DPI: 0.322 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.314 / SU Rfree Blow DPI: 0.214 / SU Rfree Cruickshank DPI: 0.218
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 147.19 Å2 / Biso mean: 43.36 Å2 / Biso min: 12.69 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.4→43.83 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.4→2.46 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
|