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Yorodumi- PDB-8bik: Crystal structure of human AMPK heterotrimer in complex with allo... -
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-Basic information
Entry | Database: PDB / ID: 8bik | ||||||
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Title | Crystal structure of human AMPK heterotrimer in complex with allosteric activator C455 | ||||||
Components |
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Keywords | SIGNALING PROTEIN / AMPK activator / allosteric activator / ADaM site / structure-based drug design / selectivity | ||||||
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 / cAMP-dependent protein kinase activity / lipid biosynthetic process / negative regulation of tubulin deacetylation / AMP-activated protein kinase activity / Macroautophagy / positive regulation of protein localization / AMP binding / cholesterol biosynthetic process / positive regulation of macroautophagy / cellular response to nutrient levels / regulation of macroautophagy / positive regulation of protein kinase activity / fatty acid homeostasis / cellular response to glucose starvation / positive regulation of autophagy / energy homeostasis / Activation of AMPK downstream of NMDARs / regulation of microtubule cytoskeleton organization / 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 / TP53 Regulates Metabolic Genes / cellular response to glucose stimulus / regulation of circadian rhythm / ADP binding / fatty acid biosynthetic process / autophagy / Wnt signaling pathway / 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 / dendrite / chromatin binding / positive regulation of gene expression / negative regulation of apoptotic process / protein kinase binding / Golgi apparatus / signal transduction / nucleoplasm / ATP binding / membrane / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.5 Å | ||||||
Authors | Schimpl, M. / Mather, K.M. / Boland, M.L. / Rivers, E.L. / Srivastava, A. / Hemsley, P. / Robinson, J. / Wan, P.T. / Hansen, J. / Read, J.A. ...Schimpl, M. / Mather, K.M. / Boland, M.L. / Rivers, E.L. / Srivastava, A. / Hemsley, P. / Robinson, J. / Wan, P.T. / Hansen, J. / Read, J.A. / Trevaskis, J.L. / Smith, D.M. | ||||||
Funding support | 1items
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Citation | Journal: Biorxiv / Year: 2024 Title: Direct beta 1/ beta 2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis Authors: Mather, K.M. / Boland, M.L. / Rivers, E.L. / Srivastava, A. / Schimpl, M. / Hemsley, P. / Robinson, J. / Wan, P. / Hansen, J. / Read, J.A. / Trevaskis, J.L. / Smith, D.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bik.cif.gz | 782.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bik.ent.gz | 635.9 KB | Display | PDB format |
PDBx/mmJSON format | 8bik.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bi/8bik ftp://data.pdbj.org/pub/pdb/validation_reports/bi/8bik | HTTPS FTP |
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-Related structure data
Related structure data | 4cffS S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-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 AD
#1: Protein | Mass: 63368.684 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAA2, AMPK, AMPK2 / Production host: Escherichia coli BL21(DE3) (bacteria) 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 BECF
#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 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9Y478 #3: Protein | Mass: 37626.289 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAG1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P54619 |
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-Non-polymers , 4 types, 491 molecules
#4: Chemical | #5: Chemical | Mass: 543.034 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H27ClN4O5S #6: Chemical | ChemComp-AMP / #7: Water | ChemComp-HOH / | |
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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: 2.55 Å3/Da / Density % sol: 51.72 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 7.2 Details: AMPK a2b1g1 (5 mg/ml: 38 uM) was combined with AMP (4-fold excess), staurosporine (1.2-fold excess) and activator 455 (3-fold excess): and crystallised at 20 C by mixing 2 ul of the protein ...Details: AMPK a2b1g1 (5 mg/ml: 38 uM) was combined with AMP (4-fold excess), staurosporine (1.2-fold excess) and activator 455 (3-fold excess): and crystallised at 20 C by mixing 2 ul of the protein solution with 1 ul of 8 % PEG3350, 0.3 M guanidine hydrochloride, 0.1 M PIPES buffer pH 7.2. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.97949 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 29, 2016 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.5→75.22 Å / Num. obs: 91016 / % possible obs: 99.9 % / Redundancy: 3.3 % / Biso Wilson estimate: 69.44 Å2 / CC1/2: 0.988 / Rmerge(I) obs: 0.069 / Rpim(I) all: 0.045 / Rrim(I) all: 0.082 / Net I/σ(I): 8.9 / Num. measured all: 300129 / Scaling rejects: 73 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdbid 4CFF Resolution: 2.5→69.52 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.941 / SU R Cruickshank DPI: 0.336 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.32 / SU Rfree Blow DPI: 0.217 / SU Rfree Cruickshank DPI: 0.223
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Displacement parameters | Biso max: 238.29 Å2 / Biso mean: 67.72 Å2 / Biso min: 22.6 Å2
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Refine analyze | Luzzati coordinate error obs: 0.31 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.5→69.52 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.52 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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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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