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2h6d

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==Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)==
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[[Image:2h6d.png|left|200px]]
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<StructureSection load='2h6d' size='340' side='right' caption='[[2h6d]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2h6d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H6D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H6D FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f15|2f15]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAA2, AMPK, AMPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h6d OCA], [http://pdbe.org/2h6d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h6d RCSB], [http://www.ebi.ac.uk/pdbsum/2h6d PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] 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. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref>
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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/h6/2h6d_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=2h6d 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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The AMP-activated protein kinase (AMPK) is a highly conserved trimeric protein complex that is responsible for energy homeostasis in eukaryotic cells. Here, a 1.9 A resolution crystal structure of the isolated kinase domain from the alpha2 subunit of human AMPK, the first from a multicellular organism, is presented. This human form adopts a catalytically inactive state with distorted ATP-binding and substrate-binding sites. The ATP site is affected by changes in the base of the activation loop, which has moved into an inhibited DFG-out conformation. The substrate-binding site is disturbed by changes within the AMPKalpha2 catalytic loop that further distort the enzyme from a catalytically active form. Similar structural rearrangements have been observed in a yeast AMPK homologue in response to the binding of its auto-inhibitory domain; restructuring of the kinase catalytic loop is therefore a conserved feature of the AMPK protein family and is likely to represent an inhibitory mechanism that is utilized during function.
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A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.,Littler DR, Walker JR, Davis T, Wybenga-Groot LE, Finerty PJ Jr, Newman E, Mackenzie F, Dhe-Paganon S Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Feb 1;66(Pt, 2):143-51. Epub 2010 Jan 27. PMID:20124709<ref>PMID:20124709</ref>
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The line below this paragraph, containing "STRUCTURE_2h6d", creates the "Structure Box" on the page.
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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or leave the SCENE parameter empty for the default display.
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{{STRUCTURE_2h6d| PDB=2h6d | SCENE= }}
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===Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2h6d" style="background-color:#fffaf0;"></div>
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==See Also==
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<!--
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*[[AMP-activated protein kinase|AMP-activated protein kinase]]
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The line below this paragraph, {{ABSTRACT_PUBMED_20124709}}, adds the Publication Abstract to the page
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== References ==
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(as it appears on PubMed at http://www.pubmed.gov), where 20124709 is the PubMed ID number.
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<references/>
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__TOC__
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{{ABSTRACT_PUBMED_20124709}}
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</StructureSection>
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[[Category: Human]]
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==About this Structure==
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2H6D is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H6D OCA].
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==Reference==
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<ref group="xtra">PMID:20124709</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Arrowsmith, C H]]
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[[Category: Bochkarev, A.]]
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[[Category: Bochkarev, A]]
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[[Category: Butler-Cole, C.]]
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[[Category: Butler-Cole, C]]
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[[Category: Dhe-Paganon, S.]]
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[[Category: Dhe-Paganon, S]]
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[[Category: Edwards, A M.]]
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[[Category: Edwards, A M]]
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[[Category: Finerty, P J.]]
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[[Category: Finerty, P J]]
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[[Category: Littler, D R.]]
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[[Category: Littler, D R]]
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[[Category: Mackenzie, F.]]
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[[Category: Mackenzie, F]]
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[[Category: Newman, E M.]]
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[[Category: Newman, E M]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Structural genomic]]
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[[Category: Sundstrom, M.]]
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[[Category: Sundstrom, M]]
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[[Category: Walker, J R.]]
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[[Category: Walker, J R]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt, J]]
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[[Category: Wybenga-Groot, L.]]
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[[Category: Wybenga-Groot, L]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Cholesterol biosynthesis]]
[[Category: Cholesterol biosynthesis]]
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[[Category: Steroid biosynthesis]]
[[Category: Steroid biosynthesis]]
[[Category: Sterol biosynthesis]]
[[Category: Sterol biosynthesis]]
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[[Category: Structural genomic]]
 
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[[Category: Structural genomics consortium]]
 
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 09:51:29 2010''
 

Current revision

Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)

2h6d, resolution 1.85Å

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