Evans sandbox 1: Difference between revisions
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{{STRUCTURE_1lvl | PDB=1lvl | SCENE= }} | {{STRUCTURE_1lvl | PDB=1lvl | SCENE= }} | ||
==General== | ==Structure and General Information== | ||
Dihydrolipoamide dehydrogenase(E3), a component of the Saccharomyces cerevisiae and mammalian [[Pyruvate dehydrogenase]] complexes (PDC), anchors an E3 homodimer inside each of the 12 pentagonal faces of the 60-mer dihydrolipoamide acetyltransferase (E2)[http://pubs.acs.org/doi/full/10.1021/bi9600254?prevSearch=%2528Dihydrolipoamide%2Bdehydrogenase%2B%2528E3%2529%2529%2BNOT%2B%255Batype%253A%2Bad%255D%2BNOT%2B%255Batype%253A%2Bacs-toc%255D&searchHistoryKey=] PDC is the enzyme in the citric acid cycle responsible for the reaction converting Pyruvate to Acetyl CoA, NAD+ to NADH and H+ and the release of carbon dioxide | Dihydrolipoamide dehydrogenase(E3), a component of the Saccharomyces cerevisiae and mammalian [[Pyruvate dehydrogenase]] complexes (PDC), anchors an E3 homodimer inside each of the 12 pentagonal faces of the 60-mer dihydrolipoamide acetyltransferase (E2)[http://pubs.acs.org/doi/full/10.1021/bi9600254?prevSearch=%2528Dihydrolipoamide%2Bdehydrogenase%2B%2528E3%2529%2529%2BNOT%2B%255Batype%253A%2Bad%255D%2BNOT%2B%255Batype%253A%2Bacs-toc%255D&searchHistoryKey=] PDC is the enzyme in the citric acid cycle responsible for the reaction converting Pyruvate to Acetyl CoA, NAD+ to NADH and H+ and the release of carbon dioxide. E3's cofactors include NAD+ and FAD, and unlike E1 and E2, there are equal subunits noncovalently bonded to the 60-meric transacetylase core in both prokaryotes and eukaryotes. The jmol image shown upon loading the page is the base subunit which is bonded to the core. | ||
E3 is common to all a-ketoacid dehydrogenase complexes. Errors in the gene coding human E3 cause combined deficiencies in a-ketoacid dehydrogenase complexes manifested by lactic acidemias and Maple Syrup Urine Disease[http://en.wikipedia.org/wiki/Maple_syrup_urine_disease]. A subset of the human E3 mutations has been suggested to occur at the homodimer interface or at the putative E3/E3BP interaction surface | E3 is common to all a-ketoacid dehydrogenase complexes. Errors in the gene coding human E3 cause combined deficiencies in a-ketoacid dehydrogenase complexes manifested by lactic acidemias and Maple Syrup Urine Disease[http://en.wikipedia.org/wiki/Maple_syrup_urine_disease]. A subset of the human E3 mutations has been suggested to occur at the homodimer interface or at the putative E3/E3BP interaction surface | ||
[[Image: pyruvate_dehydrogenase.gif|500px|left|thumb]] | [[Image: pyruvate_dehydrogenase.gif|500px|left|thumb]] | ||
E3 is synthesized as a precursor form in the cytoplasm and imported into mitochondria, and the mature E3 migrates as a 55 kDa polypeptide in SDS-PAGE though its calculated molecular mass with one molecule of FAD is 51 kDa. | |||
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[[Image: PyruvateDehydrgenaseMech1.gif|1000px|left|thumb]] | [[Image: PyruvateDehydrgenaseMech1.gif|1000px|left|thumb]] | ||
A 16-amino acid leader sequence addition changes the kinetic mechanism of human E3 so that it resembles the mixed sequential and ping-pong mechanism of [[Glutathione Reductase]]‘<ref>Kim, Hakjung Expression of cDNA Sequences Encoding Mature and Precursor Forms of Human Dihydrolipoamide Dehydrogenase in Escherichia coli. Journal of Biological Chemistry. 266, 15. 1991.</ref>’ | |||
==Regulation== | ==Regulation== | ||
The regulation of | The regulation of E3 kinetically comes through regulation of the entire Pyruvate Dehydrogenase complex. As would be expected, one of the main regulators is the presence of its product, acetyl-CoA as well as NADH. NADH competes with NAD+ with the binding site on E3, therefor regulating the entire pyruvate dehydrogenase complex when NADH is in high concentration.‘<ref>Voet, Donald et al. 2008. Fundamentals of Biochemistry. 3rd ed. p.585</ref>’ | ||