2v92

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[[Image:2v92.gif|left|200px]]
 
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==Crystal structure of the regulatory fragment of mammalian AMPK in complexes with ATP-AMP==
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The line below this paragraph, containing "STRUCTURE_2v92", creates the "Structure Box" on the page.
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<StructureSection load='2v92' size='340' side='right'caption='[[2v92]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2v92]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V92 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
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{{STRUCTURE_2v92| PDB=2v92 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v92 OCA], [https://pdbe.org/2v92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v92 RCSB], [https://www.ebi.ac.uk/pdbsum/2v92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v92 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AAKB2_HUMAN AAKB2_HUMAN] Non-catalytic 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. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v9/2v92_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v92 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound.
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'''CRYSTAL STRUCTURE OF THE REGULATORY FRAGMENT OF MAMMALIAN AMPK IN COMPLEXES WITH ATP-AMP'''
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Structural basis for AMP binding to mammalian AMP-activated protein kinase.,Xiao B, Heath R, Saiu P, Leiper FC, Leone P, Jing C, Walker PA, Haire L, Eccleston JF, Davis CT, Martin SR, Carling D, Gamblin SJ Nature. 2007 Sep 27;449(7161):496-500. Epub 2007 Sep 12. PMID:17851531<ref>PMID:17851531</ref>
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==Overview==
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AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2V92 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V92 OCA].
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</div>
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<div class="pdbe-citations 2v92" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis for AMP binding to mammalian AMP-activated protein kinase., Xiao B, Heath R, Saiu P, Leiper FC, Leone P, Jing C, Walker PA, Haire L, Eccleston JF, Davis CT, Martin SR, Carling D, Gamblin SJ, Nature. 2007 Sep 27;449(7161):496-500. Epub 2007 Sep 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17851531 17851531]
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*[[AMP-activated protein kinase 3D structures|AMP-activated protein kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Carling, D.]]
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[[Category: Carling D]]
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[[Category: Davis, C T.]]
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[[Category: Davis CT]]
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[[Category: Eccleston, J F.]]
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[[Category: Eccleston JF]]
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[[Category: Gamblin, S J.]]
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[[Category: Gamblin SJ]]
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[[Category: Haire, L.]]
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[[Category: Haire L]]
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[[Category: Heath, R.]]
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[[Category: Heath R]]
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[[Category: Jing, C.]]
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[[Category: Jing C]]
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[[Category: Leiper, F C.]]
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[[Category: Leiper FC]]
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[[Category: Leone, P.]]
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[[Category: Leone P]]
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[[Category: Martin, S R.]]
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[[Category: Martin SR]]
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[[Category: Saiu, P.]]
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[[Category: Saiu P]]
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[[Category: Walker, P A.]]
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[[Category: Walker PA]]
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[[Category: Xiao, B.]]
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[[Category: Xiao B]]
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[[Category: Atp-binding]]
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[[Category: Cbs domain]]
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[[Category: Kinase]]
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[[Category: Magnesium]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphorylation]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:24:10 2008''
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Current revision

Crystal structure of the regulatory fragment of mammalian AMPK in complexes with ATP-AMP

PDB ID 2v92

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