+Open data
-Basic information
Entry | Database: PDB / ID: 5kq5 | ||||||
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Title | AMPK bound to allosteric activator | ||||||
Components |
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Keywords | TRANSFERASE / Kinase Allosteric Activator | ||||||
Function / homology | Function and homology information eukaryotic elongation factor-2 kinase activator activity / Energy dependent regulation of mTOR by LKB1-AMPK / positive regulation of mitochondrial transcription / Regulation of TP53 Activity through Phosphorylation / Macroautophagy / TP53 Regulates Metabolic Genes / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / nail development / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / : ...eukaryotic elongation factor-2 kinase activator activity / Energy dependent regulation of mTOR by LKB1-AMPK / positive regulation of mitochondrial transcription / Regulation of TP53 Activity through Phosphorylation / Macroautophagy / TP53 Regulates Metabolic Genes / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / nail development / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / : / regulation of stress granule assembly / histone H2BS36 kinase activity / regulation of peptidyl-serine phosphorylation / cold acclimation / positive regulation of peptidyl-lysine acetylation / lipid droplet disassembly / regulation of bile acid secretion / positive regulation of fatty acid oxidation / positive regulation of skeletal muscle tissue development / CAMKK-AMPK signaling cascade / import into nucleus / regulation of vesicle-mediated transport / nucleotide-activated protein kinase complex / : / negative regulation of hepatocyte apoptotic process / tau-protein kinase / bile acid and bile salt transport / cellular response to ethanol / negative regulation of TOR signaling / protein localization to lipid droplet / protein kinase regulator activity / bile acid signaling pathway / response to caffeine / motor behavior / positive regulation of protein targeting to mitochondrion / lipid biosynthetic process / AMP-activated protein kinase activity / negative regulation of tubulin deacetylation / tau-protein kinase activity / positive regulation of protein localization / AMP binding / cholesterol biosynthetic process / fatty acid oxidation / fatty acid homeostasis / cellular response to nutrient levels / negative regulation of lipid catabolic process / positive regulation of autophagy / regulation of microtubule cytoskeleton organization / cellular response to glucose starvation / response to UV / energy homeostasis / positive regulation of gluconeogenesis / negative regulation of insulin receptor signaling pathway / negative regulation of TORC1 signaling / positive regulation of adipose tissue development / cellular response to calcium ion / positive regulation of glycolytic process / response to activity / positive regulation of glucose import / response to gamma radiation / cellular response to glucose stimulus / response to hydrogen peroxide / regulation of circadian rhythm / ADP binding / Wnt signaling pathway / fatty acid biosynthetic process / autophagy / cellular response to hydrogen peroxide / neuron cellular homeostasis / response to estrogen / cellular response to prostaglandin E stimulus / glucose metabolic process / cellular response to xenobiotic stimulus / rhythmic process / glucose homeostasis / positive regulation of cold-induced thermogenesis / cellular response to oxidative stress / cellular response to hypoxia / non-specific serine/threonine protein kinase / negative regulation of translation / protein kinase activity / nuclear speck / response to xenobiotic stimulus / apical plasma membrane / axon / protein phosphorylation / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / dendrite / chromatin binding / positive regulation of cell population proliferation / positive regulation of gene expression / protein-containing complex binding / chromatin / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / signal transduction Similarity search - Function | ||||||
Biological species | Rattus norvegicus (Norway rat) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.41 Å | ||||||
Authors | Calabrese, M.F. / Kurumbail, R.G. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated ...Title: Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy. Authors: Cameron, K.O. / Kung, D.W. / Kalgutkar, A.S. / Kurumbail, R.G. / Miller, R. / Salatto, C.T. / Ward, J. / Withka, J.M. / Bhattacharya, S.K. / Boehm, M. / Borzilleri, K.A. / Brown, J.A. / ...Authors: Cameron, K.O. / Kung, D.W. / Kalgutkar, A.S. / Kurumbail, R.G. / Miller, R. / Salatto, C.T. / Ward, J. / Withka, J.M. / Bhattacharya, S.K. / Boehm, M. / Borzilleri, K.A. / Brown, J.A. / Calabrese, M. / Caspers, N.L. / Cokorinos, E. / Conn, E.L. / Dowling, M.S. / Edmonds, D.J. / Eng, H. / Fernando, D.P. / Frisbie, R. / Hepworth, D. / Landro, J. / Mao, Y. / Rajamohan, F. / Reyes, A.R. / Rose, C.R. / Ryder, T. / Shavnya, A. / Smith, A.C. / Tu, M. / Wolford, A.C. / Xiao, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5kq5.cif.gz | 346 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5kq5.ent.gz | 275.8 KB | Display | PDB format |
PDBx/mmJSON format | 5kq5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kq/5kq5 ftp://data.pdbj.org/pub/pdb/validation_reports/kq/5kq5 | HTTPS FTP |
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-Related structure data
Related structure data | 4qfgS 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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Details | Hetero-trimer (ABC) as determined with copurification, gel-filtration, functional evidence. |
-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 57779.137 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Prkaa1, Ampk1 / Production host: Escherichia coli (E. coli) References: UniProt: P54645, non-specific serine/threonine protein kinase, [acetyl-CoA carboxylase] kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase, tau-protein kinase |
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-5'-AMP-activated protein kinase subunit ... , 2 types, 2 molecules BC
#2: Protein | Mass: 23045.273 Da / Num. of mol.: 1 / Fragment: residues 68-270 / Mutation: S108D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Prkab1 / Production host: Escherichia coli (E. coli) / References: UniProt: P80386 |
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#3: Protein | Mass: 37434.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Prkag1 / Production host: Escherichia coli (E. coli) / References: UniProt: P80385 |
-Non-polymers , 6 types, 10 molecules
#4: Chemical | ChemComp-STU / | ||||||
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#5: Chemical | ChemComp-6VT / | ||||||
#6: Chemical | ChemComp-CL / #7: Chemical | #8: Chemical | ChemComp-ADP / | #9: Chemical | ChemComp-SO4 / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.81 Å3/Da / Density % sol: 67.7 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop Details: ~750 mM Ammonium Acetate, 500 mM Lithium Sulfate, 100 mM trisodium citrate, 1% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 26, 2012 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3.4→30 Å / Num. obs: 25248 / % possible obs: 96.2 % / Redundancy: 4.2 % / Biso Wilson estimate: 89.73 Å2 / Rmerge(I) obs: 0.138 / Χ2: 1.375 / Net I/av σ(I): 12.371 / Net I/σ(I): 7.3 / Num. measured all: 105416 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4QFG Resolution: 3.41→29.9 Å / Cor.coef. Fo:Fc: 0.9079 / Cor.coef. Fo:Fc free: 0.8672 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.44 / SU Rfree Cruickshank DPI: 0.443
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Displacement parameters | Biso max: 216.2 Å2 / Biso mean: 115.34 Å2 / Biso min: 57.94 Å2
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Refine analyze | Luzzati coordinate error obs: 0.47 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.41→29.9 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.41→3.55 Å / Total num. of bins used: 13
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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