| Structural highlights
Function
PDC1_YEAST Major of three pyruvate decarboxylases (PDC1, PDC5, PDC6) implicated in the nonoxidative conversion of pyruvate to acetaldehyde and carbon dioxide during alcoholic fermentation. Most of the produced acetaldehyde is subsequently reduced to ethanol, but some is required for cytosolic acetyl-CoA production for biosynthetic pathways. The enzyme is also one of five 2-oxo acid decarboxylases (PDC1, PDC5, PDC6, ARO10, and THI3) able to decarboxylate more complex 2-oxo acids (alpha-ketoacids) than pyruvate, which seem mainly involved in amino acid catabolism. Here the enzyme catalyzes the decarboxylation of amino acids, which, in a first step, have been transaminated to the corresponding 2-oxo acids. In a third step, the resulting aldehydes are reduced to alcohols, collectively referred to as fusel oils or alcohols. Its preferred substrates are the transaminated amino acids valine, isoleucine, phenylalanine, and tryptophan, whereas leucine is no substrate. In a side-reaction the carbanionic intermediate (or active aldehyde) generated by decarboxylation or by activation of an aldehyde can react with an aldehyde via condensation (or carboligation) yielding a 2-hydroxy ketone, collectively called acyloins.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The mechanism by which the enzyme pyruvate decarboxylase from two yeast species is activated allosterically has been elucidated. A total of seven three-dimensional structures of the enzyme, of enzyme variants, or of enzyme complexes from two yeast species, three of them reported here for the first time, provide detailed atomic resolution snapshots along the activation coordinate. The prime event is the covalent binding of the substrate pyruvate to the side chain of cysteine 221, thus forming a thiohemiketal. This reaction causes the shift of a neighboring amino acid, which eventually leads to the rigidification of two otherwise flexible loops, one of which provides two histidine residues necessary to complete the enzymatically competent active site architecture. The structural data are complemented and supported by kinetic investigations and binding studies, providing a consistent picture of the structural changes occurring upon enzyme activation.
Covalently bound substrate at the regulatory site of yeast pyruvate decarboxylases triggers allosteric enzyme activation.,Kutter S, Weiss MS, Wille G, Golbik R, Spinka M, Konig S J Biol Chem. 2009 May 1;284(18):12136-44. Epub 2009 Feb 26. PMID:19246454[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lehmann H, Fischer G, Hubner G, Kohnert KD, Schellenberger A. The influence of steric and electronic parameters on the substrate behavior of -oxo acids to yeast pyruvate decarboxylase. Eur J Biochem. 1973 Jan 3;32(1):83-7. PMID:4687392
- ↑ Liesen T, Hollenberg CP, Heinisch JJ. ERA, a novel cis-acting element required for autoregulation and ethanol repression of PDC1 transcription in Saccharomyces cerevisiae. Mol Microbiol. 1996 Aug;21(3):621-32. PMID:8866484
- ↑ Dickinson JR, Lanterman MM, Danner DJ, Pearson BM, Sanz P, Harrison SJ, Hewlins MJ. A 13C nuclear magnetic resonance investigation of the metabolism of leucine to isoamyl alcohol in Saccharomyces cerevisiae. J Biol Chem. 1997 Oct 24;272(43):26871-8. PMID:9341119
- ↑ Dickinson JR, Harrison SJ, Hewlins MJ. An investigation of the metabolism of valine to isobutyl alcohol in Saccharomyces cerevisiae. J Biol Chem. 1998 Oct 2;273(40):25751-6. PMID:9748245
- ↑ Flikweert MT, de Swaaf M, van Dijken JP, Pronk JT. Growth requirements of pyruvate-decarboxylase-negative Saccharomyces cerevisiae. FEMS Microbiol Lett. 1999 May 1;174(1):73-9. PMID:10234824
- ↑ Eberhardt I, Cederberg H, Li H, Konig S, Jordan F, Hohmann S. Autoregulation of yeast pyruvate decarboxylase gene expression requires the enzyme but not its catalytic activity. Eur J Biochem. 1999 May;262(1):191-201. PMID:10231381
- ↑ Dickinson JR, Harrison SJ, Dickinson JA, Hewlins MJ. An investigation of the metabolism of isoleucine to active Amyl alcohol in Saccharomyces cerevisiae. J Biol Chem. 2000 Apr 14;275(15):10937-42. PMID:10753893
- ↑ Neuser F, Zorn H, Berger RG. Generation of odorous acyloins by yeast pyruvate decarboxylases and their occurrence in sherry and soy sauce. J Agric Food Chem. 2000 Dec;48(12):6191-5. PMID:11141278
- ↑ Dickinson JR, Salgado LE, Hewlins MJ. The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae. J Biol Chem. 2003 Mar 7;278(10):8028-34. Epub 2002 Dec 23. PMID:12499363 doi:10.1074/jbc.M211914200
- ↑ Vuralhan Z, Morais MA, Tai SL, Piper MD, Pronk JT. Identification and characterization of phenylpyruvate decarboxylase genes in Saccharomyces cerevisiae. Appl Environ Microbiol. 2003 Aug;69(8):4534-41. PMID:12902239
- ↑ Kutter S, Weiss MS, Wille G, Golbik R, Spinka M, Konig S. Covalently bound substrate at the regulatory site of yeast pyruvate decarboxylases triggers allosteric enzyme activation. J Biol Chem. 2009 May 1;284(18):12136-44. Epub 2009 Feb 26. PMID:19246454 doi:10.1074/jbc.M806228200
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