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Pyruvate dehydrogenase kinase
From Proteopedia
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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'> | <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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== Function == | == Function == | ||
'''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. | '''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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== Structural highlights == | == Structural highlights == | ||
| - | <scene name='48/485629/Cv/ | + | <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>. |
</StructureSection> | </StructureSection> | ||
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==3D structures of pyruvate dehydrogenase kinase== | ==3D structures of pyruvate dehydrogenase kinase== | ||
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*PDK isozyme 2 | *PDK isozyme 2 | ||
| - | **[[1jm6]] – PDK2 + ADP – rat<br /> | ||
**[[2btz]] – hPDK2 <br /> | **[[2btz]] – hPDK2 <br /> | ||
**[[2bu2]] – hPDK2 + benzonitrile derivative + ATP<br /> | **[[2bu2]] – hPDK2 + benzonitrile derivative + ATP<br /> | ||
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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 /> | ||
| - | **[[4mp2]], [[4mp7]], [[4mpc]], [[4mpe]], [[4mpn]], [[4v25]], [[4v26]], [[5j6a]], [[5j71]], [[5m4k]], [[5m4m]], [[5m4n]], [[5m4p]] – hPDK2 + inhibitor<br /> | + | **[[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 /> |
| - | **[[3crk]], [[3crl]] – hPDK2 + pyruvate dehydrogenase E2 | + | **[[3crk]], [[3crl]] – hPDK2 + pyruvate dehydrogenase E2<br /> |
| + | **[[1jm6]] – PDK2 + ADP – rat<br /> | ||
*PDK isozyme 3 | *PDK isozyme 3 | ||
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**[[2e0a]] – hPDK4 + AMPPNP<br /> | **[[2e0a]] – hPDK4 + AMPPNP<br /> | ||
**[[2zkj]], [[3d2r]] – hPDK4 + ADP<BR /> | **[[2zkj]], [[3d2r]] – hPDK4 + ADP<BR /> | ||
| + | **[[7ea0]], [[7eat]], [[7ebb]], [[7ebg]] – hPDK4 + inhibitor<br /> | ||
**[[2zdx]], [[2zdy]] – hPDK4 (mutant) + inhibitor | **[[2zdx]], [[2zdy]] – hPDK4 (mutant) + inhibitor | ||
}} | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Topic Page]] | [[Category: Topic Page]] | ||
Current revision
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3D structures of pyruvate dehydrogenase kinase
Updated on 04-October-2023
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
