2pnr
From Proteopedia
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| - | [[Image:2pnr.png|left|200px]] | ||
| - | + | ==Crystal Structure of the asymmetric Pdk3-l2 Complex== | |
| + | <StructureSection load='2pnr' size='340' side='right'caption='[[2pnr]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2pnr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PNR 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]] 2.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</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=2pnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pnr OCA], [https://pdbe.org/2pnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pnr RCSB], [https://www.ebi.ac.uk/pdbsum/2pnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pnr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pnr_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=2pnr ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A homodimer of pyruvate dehydrogenase kinase (PDHK) is an integral part of pyruvate dehydrogenase complex (PDC) to which it is anchored primarily through the inner lipoyl-bearing domains (L2) of transacetylase component. The catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the "symmetric" and "asymmetric" modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively. Whereas the structure of the symmetric PDHK/L2 complex was reported, the structural organization and functional role of the asymmetric complex remain obscure. Here, we report the crystal structure of the asymmetric PDHK3/L2 complex that reveals several functionally important features absent from the previous structures. First, the PDHK3 subunits have distinct conformations: one subunit exhibits "open" and the other "closed" configuration of the putative substrate-binding cleft. Second, access to the closed cleft is additionally restricted by local unwinding of the adjacent alpha-helix. Modeling indicates that the target peptide might gain access to the PDHK active center through the open but not through the closed cleft. Third, the ATP-binding loop in one PDHK3 subunit adopts an open conformation, implying that the nucleotide loading into the active site is mediated by the inactive "pre-insertion" binding mode. Altogether our data suggest that the asymmetric complex represents a physiological state in which binding of a single L2-domain activates one of the PDHK protomers while inactivating another. Thus, the L2-domains likely act not only as the structural anchors but also modulate the catalytic cycle of PDHK. | ||
| - | + | Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications.,Devedjiev Y, Steussy CN, Vassylyev DG J Mol Biol. 2007 Jul 13;370(3):407-16. Epub 2007 May 10. PMID:17532006<ref>PMID:17532006</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2pnr" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Pyruvate dehydrogenase kinase|Pyruvate dehydrogenase kinase]] | *[[Pyruvate dehydrogenase kinase|Pyruvate dehydrogenase kinase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Devedjiev Y]] |
| - | [[Category: | + | [[Category: Steussy CN]] |
| - | [[Category: | + | [[Category: Vassylyev DG]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of the asymmetric Pdk3-l2 Complex
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