Pyruvate dehydrogenase kinase

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{{STRUCTURE_2q8g| PDB=2q8g | SIZE=400| SCENE= |right|CAPTION=Human pyruvate dehydrogenase kinase isozyme 1 complex with ADP and K+ ion [[2q8g]] }}
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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'>
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__TOC__
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== Function ==
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Please use the "3D" button above this box to insert a Jmol applet (molecule) on this page.
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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.
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Or use the four-green-boxes-button to insert scrollable text adjacent
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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.
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== Relevance ==
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Inhibition of PDK decreases the damage caused by heart ischemia and are used in diabetes and cancer patients<ref>PMID:17310282</ref><ref>PMID:23471124</ref>.
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== Structural highlights ==
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<scene name='48/485629/Cv/11'>The active site cleft of PDK4 binds AMPPNP</scene><ref>PMID:21904029</ref>. Water molecules are shown as red spheres. <scene name='48/485629/Cv/12'>Mg coordination site</scene>.
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</StructureSection>
==3D structures of pyruvate dehydrogenase kinase==
==3D structures of pyruvate dehydrogenase kinase==
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'''PDK isozyme 1'''
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*PDK isozyme 1
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**[[2q8f ]]– hPDK1 – human<br />
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**[[2q8g]] – hPDK1 + drug<br />
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**[[2q8h]] – hPDK1 + dichloro-acetic acid
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[[2q8f ]]– hPDK1 – human<br />
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*PDK isozyme 2
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[[2q8g]] – hPDK1 + drug<br />
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[[2q8h]] – hPDK1 + dichloro-acetic acid
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'''PDK isozyme 2'''
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**[[2btz]] – hPDK2 <br />
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**[[2bu2]] – hPDK2 + benzonitrile derivative + ATP<br />
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**[[2bu5]] - hPDK2 + benzonitrile derivative<br />
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**[[2bu6]] - hPDK2 + propanamide derivative<br />
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**[[2bu7]] - hPDK2 + acetamide derivative<br />
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**[[2bu8]] - hPDK2 + dichloro-acetic acid + ADP<BR />
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**[[4mp2]], [[4mp7]], [[4mpc]], [[4mpe]], [[4mpn]], [[4v25]], [[4v26]], [[5j6a]], [[5j71]], [[5m4k]], [[5m4m]], [[5m4n]], [[5m4p]], [[6lil]], [[6lio]], [[6lin]], [[6tmz]], [[6tmp]], [[6tmq]], [[6tn0]], [[6tn2]], [[7ebh]], [[7eas]], [[7vbu]], [[7vbv]], [[7vbx]] – hPDK2 + inhibitor<br />
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**[[3crk]], [[3crl]] – hPDK2 + pyruvate dehydrogenase E2<br />
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**[[1jm6]] – PDK2 + ADP – rat<br />
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[[1jm6]] – PDK2 + ADP – rat<br />
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*PDK isozyme 3
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[[2btz]] – hPDK2 <br />
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[[2bu2]] – hPDK2 + benzonitrile derivative + ATP<br />
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[[2bu5]] - hPDK2 + benzonitrile derivative<br />
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[[2bu6]] - hPDK2 + propanamide derivative<br />
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[[2bu7]] - hPDK2 + acetamide derivative<br />
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[[2bu8]] - hPDK2 + dichloro-acetic acid + ADP<BR />
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[[3crk]], [[3crl]] – hPDK2 + acetyltransferase component of pyruvate dehydrogenase complex
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'''PDK isozyme 3'''
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**[[1y8n]], [[1y8o]], [[1y8p]], [[2pnr]] – hPDK3 + acetyltransferase component of pyruvate dehydrogenase complex <br />
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**[[2q8i]] – hPDK3 + radicicol
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[[1y8n]], [[1y8o]], [[1y8p]], [[2pnr]] – hPDK3 + acetyltransferase component of pyruvate dehydrogenase complex <br />
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*PDK isozyme 4
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[[2q8i]] – hPDK3 + radicicol
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'''PDK isozyme 4'''
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**[[2e0a]] – hPDK4 + AMPPNP<br />
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**[[2zkj]], [[3d2r]] – hPDK4 + ADP<BR />
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**[[7ea0]], [[7eat]], [[7ebb]], [[7ebg]] – hPDK4 + inhibitor<br />
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**[[2zdx]], [[2zdy]] – hPDK4 (mutant) + inhibitor
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}}
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== References ==
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<references/>
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[[2e0a]] – hPDK4 + AMPPNP<br />
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[[Category: Topic Page]]
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[[2zkj]], [[3d2r]] – hPDK4 + ADP<BR />
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[[2zdx]], [[2zdy]] – hPDK4 (mutant) + inhibitor
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Current revision

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 04-October-2023

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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