+Open data
-Basic information
Entry | Database: PDB / ID: 4zhx | ||||||
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Title | Novel binding site for allosteric activation of AMPK | ||||||
Components |
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Keywords | TRANSFERASE / serine/threonine kinase / allosteric activation / nucleotide-binding | ||||||
Function / homology | Function and homology information [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / nail development / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / : / regulation of stress granule assembly / histone H2BS36 kinase activity / AMPK inhibits chREBP transcriptional activation activity / positive regulation of peptidyl-lysine acetylation / lipid droplet disassembly / Lipophagy ...[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / nail development / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / : / regulation of stress granule assembly / histone H2BS36 kinase activity / AMPK inhibits chREBP transcriptional activation activity / positive regulation of peptidyl-lysine acetylation / lipid droplet disassembly / Lipophagy / import into nucleus / cAMP-dependent protein kinase regulator activity / nucleotide-activated protein kinase complex / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine metabolism / negative regulation of hepatocyte apoptotic process / protein kinase regulator activity / protein localization to lipid droplet / negative regulation of TOR signaling / response to muscle activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of glycolytic process / Nuclear events mediated by NFE2L2 / lipid biosynthetic process / cAMP-dependent protein kinase activity / AMP-activated protein kinase activity / negative regulation of tubulin deacetylation / Macroautophagy / positive regulation of protein localization / AMP binding / cholesterol biosynthetic process / cellular response to nutrient levels / positive regulation of macroautophagy / positive regulation of protein kinase activity / regulation of macroautophagy / fatty acid homeostasis / cellular response to glucose starvation / positive regulation of autophagy / energy homeostasis / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / negative regulation of TORC1 signaling / cellular response to calcium ion / protein serine/threonine/tyrosine kinase activity / positive regulation of glycolytic process / Translocation of SLC2A4 (GLUT4) to the plasma membrane / cellular response to glucose stimulus / TP53 Regulates Metabolic Genes / regulation of circadian rhythm / ADP binding / Wnt signaling pathway / fatty acid biosynthetic process / autophagy / cytoplasmic stress granule / cellular response to prostaglandin E stimulus / rhythmic process / cellular response to xenobiotic stimulus / glucose homeostasis / positive regulation of cold-induced thermogenesis / cellular response to oxidative stress / spermatogenesis / Regulation of TP53 Activity through Phosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / nuclear speck / axon / protein phosphorylation / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / chromatin binding / dendrite / positive regulation of gene expression / negative regulation of apoptotic process / protein kinase binding / Golgi apparatus / signal transduction / nucleoplasm / ATP binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.99 Å | ||||||
Authors | Langendorf, C.G. / Ngoei, K.R. / Issa, S.M.A. / Ling, N. / Gorman, M.A. / Parker, M.W. / Sakamoto, K. / Scott, J.W. / Oakhill, J.S. / Kemp, B.E. | ||||||
Citation | Journal: Nat Commun / Year: 2016 Title: Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Authors: Langendorf, C.G. / Ngoei, K.R. / Scott, J.W. / Ling, N.X. / Issa, S.M. / Gorman, M.A. / Parker, M.W. / Sakamoto, K. / Oakhill, J.S. / Kemp, B.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4zhx.cif.gz | 758.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4zhx.ent.gz | 616.5 KB | Display | PDB format |
PDBx/mmJSON format | 4zhx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4zhx_validation.pdf.gz | 2.3 MB | Display | wwPDB validaton report |
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Full document | 4zhx_full_validation.pdf.gz | 2.3 MB | Display | |
Data in XML | 4zhx_validation.xml.gz | 63.8 KB | Display | |
Data in CIF | 4zhx_validation.cif.gz | 85.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zh/4zhx ftp://data.pdbj.org/pub/pdb/validation_reports/zh/4zhx | HTTPS FTP |
-Related structure data
Related structure data | 5ezvC 4cfeS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AC
#1: Protein | Mass: 63918.051 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAA2, AMPK, AMPK2 / Plasmid: pETDuet-1 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 (DE3) References: UniProt: P54646, non-specific serine/threonine protein kinase, [acetyl-CoA carboxylase] kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase |
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-5'-AMP-activated protein kinase subunit ... , 2 types, 4 molecules BDEF
#2: Protein | Mass: 30504.299 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAB1, AMPK / Plasmid: RSFDuet-1 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 (DE3) / References: UniProt: Q9Y478 #3: Protein | Mass: 38225.914 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAG1 / Plasmid: pETDuet-1 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 (DE3) / References: UniProt: P54619 |
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-Non-polymers , 5 types, 145 molecules
#4: Chemical | #5: Chemical | #6: Chemical | #7: Chemical | #8: Water | ChemComp-HOH / | |
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-Details
Sequence details | The D271G variant has been previously reported and can be found in the uniprot entry for AMPK alpha- ...The D271G variant has been previously reported and can be found in the uniprot entry for AMPK alpha-2 (P54646 - AAPK2_HUMAN) in the experimental info section. |
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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: 2.72 Å3/Da / Density % sol: 54.75 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.2 Details: 8 % PEG 3350, 0.1 M MgCl2, 1.0 % glucose, 0.001 % cocamidopropyl betaine, 0.1 M imidazole |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å | ||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Feb 6, 2015 | ||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 2.99→48.66 Å / Num. obs: 56598 / % possible obs: 98.8 % / Redundancy: 3.2 % / Biso Wilson estimate: 83.79 Å2 / CC1/2: 0.976 / Rmerge(I) obs: 0.107 / Rpim(I) all: 0.071 / Net I/σ(I): 8.1 / Num. measured all: 183106 / Scaling rejects: 229 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Redundancy: 3.2 % / Rejects: _
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4CFE Resolution: 2.99→43.78 Å / Cor.coef. Fo:Fc: 0.8851 / Cor.coef. Fo:Fc free: 0.8649 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.359
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Displacement parameters | Biso max: 229.33 Å2 / Biso mean: 69.7 Å2 / Biso min: 14.97 Å2
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Refine analyze | Luzzati coordinate error obs: 0.504 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.99→43.78 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.99→3.07 Å / Total num. of bins used: 20
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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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