1jm6

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

• Pyruvate dehydrogenase kinase

References

1. ↑ 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
2. ↑ 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
3. ↑ 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/
4. ↑ 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
5. ↑ 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