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- | [[Image:1jm6.jpg|left|200px]] | |
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- | {{Structure
| + | ==Pyruvate dehydrogenase kinase, isozyme 2, containing ADP== |
- | |PDB= 1jm6 |SIZE=350|CAPTION= <scene name='initialview01'>1jm6</scene>, resolution 2.50Å
| + | <StructureSection load='1jm6' size='340' side='right'caption='[[1jm6]], [[Resolution|resolution]] 2.50Å' scene=''> |
- | |SITE=
| + | == Structural highlights == |
- | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | + | <table><tr><td colspan='2'>[[1jm6]] is a 2 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=1JM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JM6 FirstGlance]. <br> |
- | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span>
| + | </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> |
- | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
- | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jm6 OCA], [https://pdbe.org/1jm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jm6 RCSB], [https://www.ebi.ac.uk/pdbsum/1jm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jm6 ProSAT]</span></td></tr> |
- | |RELATEDENTRY=
| + | </table> |
- | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jm6 OCA], [http://www.ebi.ac.uk/pdbsum/1jm6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jm6 RCSB]</span>
| + | == Function == |
- | }}
| + | [https://www.uniprot.org/uniprot/PDK2_RAT PDK2_RAT] Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.<ref>PMID:7961963</ref> <ref>PMID:11486000</ref> <ref>PMID:14641018</ref> <ref>PMID:12573248</ref> <ref>PMID:22910903</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/jm/1jm6_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1jm6 ConSurf]. |
| + | <div style="clear:both"></div> |
| | | |
- | '''Pyruvate dehydrogenase kinase, isozyme 2, containing ADP'''
| + | ==See Also== |
- | | + | *[[Pyruvate dehydrogenase kinase|Pyruvate dehydrogenase kinase]] |
- | | + | == References == |
- | ==Overview== | + | <references/> |
- | The structure of mitochondrial pyruvate dehydrogenase kinase isozyme 2 is of interest because it represents a family of serine-specific protein kinases that lack sequence similarity with all other eukaryotic protein kinases. Similarity exists instead with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases. The 2.5-A crystal structure reported here reveals that pyruvate dehydrogenase kinase isozyme 2 has two domains of about the same size. The N-terminal half is dominated by a bundle of four amphipathic alpha-helices, whereas the C-terminal half is folded into an alpha/beta sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very similar to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinases and ATPases.
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | [[Category: Large Structures]] |
- | 1JM6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JM6 OCA].
| + | |
- | | + | |
- | ==Reference==
| + | |
- | Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase., Steussy CN, Popov KM, Bowker-Kinley MM, Sloan RB Jr, Harris RA, Hamilton JA, J Biol Chem. 2001 Oct 5;276(40):37443-50. Epub 2001 Aug 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11483605 11483605]
| + | |
| [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
- | [[Category: Single protein]]
| + | [[Category: Bowker-Kinley MM]] |
- | [[Category: [Pyruvate dehydrogenase (acetyl-transferring)] kinase]]
| + | [[Category: Hamilton JA]] |
- | [[Category: Bowker-Kinley, M M.]] | + | [[Category: Harris RA]] |
- | [[Category: Hamilton, J A.]] | + | [[Category: Popov KM]] |
- | [[Category: Harris, R A.]] | + | [[Category: Sloan RB]] |
- | [[Category: Popov, K M.]] | + | [[Category: Steussy CN]] |
- | [[Category: Sloan, R B.]] | + | |
- | [[Category: Steussy, C N.]] | + | |
- | [[Category: kinase]]
| + | |
- | [[Category: mitochondion]]
| + | |
- | [[Category: serine kinase]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:35:41 2008''
| + | |
| Structural highlights
Function
PDK2_RAT Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Popov KM, Kedishvili NY, Zhao Y, Gudi R, Harris RA. Molecular cloning of the p45 subunit of pyruvate dehydrogenase kinase. J Biol Chem. 1994 Nov 25;269(47):29720-4. PMID:7961963
- ↑ Korotchkina LG, Patel MS. Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem. 2001 Oct 5;276(40):37223-9. Epub 2001 Aug 2. PMID:11486000 doi:10.1074/jbc.M103069200
- ↑ Mayers RM, Butlin RJ, Kilgour E, Leighton B, Martin D, Myatt J, Orme JP, Holloway BR. AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochem Soc Trans. 2003 Dec;31(Pt 6):1165-7. PMID:14641018 doi:10.1042/
- ↑ Boulatnikov I, Popov KM. Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase. Biochim Biophys Acta. 2003 Feb 21;1645(2):183-92. PMID:12573248
- ↑ Hurd TR, Collins Y, Abakumova I, Chouchani ET, Baranowski B, Fearnley IM, Prime TA, Murphy MP, James AM. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species. J Biol Chem. 2012 Oct 12;287(42):35153-60. doi: 10.1074/jbc.M112.400002. Epub, 2012 Aug 21. PMID:22910903 doi:10.1074/jbc.M112.400002
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