+Open data
-Basic information
Entry | Database: PDB / ID: 4rch | ||||||
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Title | Discovery of 2-Pyridyl Ureas as Glucokinase Activators | ||||||
Components | Glucokinase | ||||||
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 / calcium ion import / cellular response to leptin stimulus / 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 / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Voegtli, W. / Vigers, G.P.A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: Discovery of 2-pyridylureas as glucokinase activators. Authors: Hinklin, R.J. / Aicher, T.D. / Anderson, D.A. / Baer, B.R. / Boyd, S.A. / Condroski, K.R. / DeWolf, W.E. / Kraser, C.F. / McVean, M. / Rhodes, S.P. / Sturgis, H.L. / Voegtli, W.C. / Williams, L. / Houze, J.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4rch.cif.gz | 102.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4rch.ent.gz | 77.9 KB | Display | PDB format |
PDBx/mmJSON format | 4rch.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rc/4rch ftp://data.pdbj.org/pub/pdb/validation_reports/rc/4rch | HTTPS FTP |
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-Related structure data
Related structure data | 4mleS 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: 53026.219 Da / Num. of mol.: 1 / Fragment: UNP residues 16-465 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, glucokinase |
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#2: Sugar | ChemComp-GLC / |
#3: Chemical | ChemComp-3LZ / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.81 Å3/Da / Density % sol: 56.25 % |
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Crystal grow | Temperature: 300 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 100 mM Hepes, pH 7.0, 28% PEG 1500, 5% glycerol, 50 mM glucose, VAPOR DIFFUSION, HANGING DROP, temperature 300K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 0.97946 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 14, 2010 / Details: Rh coated flat mirror |
Radiation | Monochromator: Side scattering I-beam bent single crystal; asymmetric cut 4.9650 deg. Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→29.19 Å / Num. all: 28458 / Num. obs: 28432 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 9.99 % / Rmerge(I) obs: 0.125 / Rsym value: 0.119 / Net I/σ(I): 8.08 |
Reflection shell | Resolution: 2.3→2.42 Å / Redundancy: 10.42 % / Rmerge(I) obs: 0.285 / Mean I/σ(I) obs: 2.8 / Num. unique all: 4054 / Rsym value: 0.285 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 4MLE Resolution: 2.3→29.19 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.917 / SU B: 6.648 / SU ML: 0.162 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.288 / ESU R Free: 0.228 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 58.174 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→29.19 Å
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