2q8i: Difference between revisions

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<StructureSection load='2q8i' size='340' side='right'caption='[[2q8i]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='2q8i' size='340' side='right'caption='[[2q8i]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2q8i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q8f|2q8f]], [[2q8g|2q8g]], [[2q8h|2q8h]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDK3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span></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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [https://pdbe.org/2q8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [https://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i ProSAT]</span></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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [https://pdbe.org/2q8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [https://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.  Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[https://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
== Function ==
== 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> [[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chuang, D T]]
[[Category: Chuang DT]]
[[Category: Chuang, J L]]
[[Category: Chuang JL]]
[[Category: Kato, M]]
[[Category: Kato M]]
[[Category: Li, J]]
[[Category: Li J]]
[[Category: Ghkl atpase/kinase family]]
[[Category: Mitochondrial kinase]]
[[Category: Pyruvate dehydrogenase complex]]
[[Category: Radicicol]]
[[Category: Transferase]]

Revision as of 11:25, 30 August 2023

Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol

2q8i, resolution 2.60Å

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