4qfr
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of AMPK in complex with Cl-A769662 activator and STAUROSPORINE inhibitor== | |
| + | <StructureSection load='4qfr' size='340' side='right'caption='[[4qfr]], [[Resolution|resolution]] 3.34Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4qfr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QFR FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.34Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32J:2-CHLORO-4-HYDROXY-3-(2-HYDROXYBIPHENYL-4-YL)-6-OXO-6,7-DIHYDROTHIENO[2,3-B]PYRIDINE-5-CARBONITRILE'>32J</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qfr OCA], [https://pdbe.org/4qfr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qfr RCSB], [https://www.ebi.ac.uk/pdbsum/4qfr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qfr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AAKG1_RAT AAKG1_RAT] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:17851531</ref> <ref>PMID:21399626</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | AMP-activated protein kinase (AMPK) is a principal metabolic regulator affecting growth and response to cellular stress. Comprised of catalytic and regulatory subunits, each present in multiple forms, AMPK is best described as a family of related enzymes. In recent years, AMPK has emerged as a desirable target for modulation of numerous diseases, yet clinical therapies remain elusive. Challenges result, in part, from an incomplete understanding of the structure and function of full-length heterotrimeric complexes. In this work, we provide the full-length structure of the widely expressed alpha1beta1gamma1 isoform of mammalian AMPK, along with detailed kinetic and biophysical characterization. We characterize binding of the broadly studied synthetic activator A769662 and its analogs. Our studies follow on the heels of the recent disclosure of the alpha2beta1gamma1 structure and provide insight into the distinct molecular mechanisms of AMPK regulation by AMP and A769662. | ||
| - | + | Structural Basis for AMPK Activation: Natural and Synthetic Ligands Regulate Kinase Activity from Opposite Poles by Different Molecular Mechanisms.,Calabrese MF, Rajamohan F, Harris MS, Caspers NL, Magyar R, Withka JM, Wang H, Borzilleri KA, Sahasrabudhe PV, Hoth LR, Geoghegan KF, Han S, Brown J, Subashi TA, Reyes AR, Frisbie RK, Ward J, Miller RA, Landro JA, Londregan AT, Carpino PA, Cabral S, Smith AC, Conn EL, Cameron KO, Qiu X, Kurumbail RG Structure. 2014 Aug 5;22(8):1161-72. doi: 10.1016/j.str.2014.06.009. Epub 2014, Jul 24. PMID:25066137<ref>PMID:25066137</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4qfr" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[AMP-activated protein kinase 3D structures|AMP-activated protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Calabrese MF]] | ||
| + | [[Category: Kurumbail RG]] | ||
Current revision
Structure of AMPK in complex with Cl-A769662 activator and STAUROSPORINE inhibitor
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