Pyruvate dehydrogenase kinase

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<StructureSection load='' size='450' side='right' caption='Human pyruvate dehydrogenase kinase isozyme 4 dimer complex with AMPPNP and Mg+2 ion (green) (PDB entry [[2e0a]])' scene='48/485629/Cv/1'>
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<StructureSection load='' size='350' side='right' caption='Human pyruvate dehydrogenase kinase isozyme 4 dimer complex with AMPPNP and Mg+2 ion (green) (PDB entry [[2e0a]])' scene='48/485629/Cv/1'>
== Function ==
== Function ==
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'''Pyruvate dehydrogenase kinase''' (PDK) is part of the pyruvate dehydrogenase complex. This complex is located in the mitochondria and converts pyruvate to acetyl-CoA as part of the citric acid cycle. PDK phosphphorylates serine residues on pyruvate dehydrogenase using ATP. There are 4 isozymes of PDK. The isozymes differ in length, activity and phosphorylation sites<ref>PMID:11486000</ref>.
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'''Pyruvate dehydrogenase kinase''' (PDK) is part of the pyruvate dehydrogenase complex. This complex is located in the mitochondria and converts pyruvate to acetyl-CoA as part of the citric acid cycle. PDK phosphphorylates serine residues on pyruvate dehydrogenase using ATP. There are 4 isozymes of PDK. The isozymes differ in length, activity and phosphorylation sites<ref>PMID:11486000</ref>. PDK1 is abundant in heart cells. PDK2 is abundant in mitochondria. PDK3 is abundant in testis. PDK4 is abundant in muscle and heart.
== Relevance ==
== Relevance ==
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**[[2bu7]] - hPDK2 + acetamide derivative<br />
**[[2bu7]] - hPDK2 + acetamide derivative<br />
**[[2bu8]] - hPDK2 + dichloro-acetic acid + ADP<BR />
**[[2bu8]] - hPDK2 + dichloro-acetic acid + ADP<BR />
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**[[4mp2]], [[4mp7]], [[4mpc]], [[4mpe]], [[4mpn]], [[4v25]], [[4v26]], [[5j6a]], [[5j71]] – hPDK2 + inhibitor<br />
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**[[4mp2]], [[4mp7]], [[4mpc]], [[4mpe]], [[4mpn]], [[4v25]], [[4v26]], [[5j6a]], [[5j71]], [[5m4k]], [[5m4m]], [[5m4n]], [[5m4p]] – hPDK2 + inhibitor<br />
**[[3crk]], [[3crl]] – hPDK2 + pyruvate dehydrogenase E2
**[[3crk]], [[3crl]] – hPDK2 + pyruvate dehydrogenase E2

Revision as of 08:51, 30 August 2018

Human pyruvate dehydrogenase kinase isozyme 4 dimer complex with AMPPNP and Mg+2 ion (green) (PDB entry 2e0a)

Drag the structure with the mouse to rotate

3D structures of pyruvate dehydrogenase kinase

Updated on 30-August-2018

References

  1. ↑ 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
  2. ↑ Roche TE, Hiromasa Y. Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer. Cell Mol Life Sci. 2007 Apr;64(7-8):830-49. PMID:17310282 doi:10.1007/s00018-007-6380-z
  3. ↑ Sutendra G, Michelakis ED. Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Front Oncol. 2013 Mar 7;3:38. doi: 10.3389/fonc.2013.00038. eCollection 2013. PMID:23471124 doi:http://dx.doi.org/10.3389/fonc.2013.00038
  4. ↑ Kukimoto-Niino M, Tokmakov A, Terada T, Ohbayashi N, Fujimoto T, Gomi S, Shiromizu I, Kawamoto M, Matsusue T, Shirouzu M, Yokoyama S. Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4. Acta Crystallogr D Biol Crystallogr. 2011 Sep;67(Pt 9):763-73. doi:, 10.1107/S090744491102405X. Epub 2011 Aug 9. PMID:21904029 doi:10.1107/S090744491102405X

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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