2vk1
From Proteopedia
Crystal structure of the Saccharomyces cerevisiae pyruvate decarboxylase variant D28A in complex with its substrate
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 PubMedThe 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 AlsoReferences
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Categories: Atcc 18824 | Pyruvate decarboxylase | Konig, S | Kutter, S | Weik, M | Weiss, M S | Acetylation | Allosteric enzyme | Asymmetric active site | Branched-chain amino acid catabolism | Cytoplasm | Decarboxylase | Dimer of dimer | Lyase | Magnesium | Metal-binding | Nucleus | Phenylalanine catabolism | Phosphorylation | Pyruvate | Substrate activation | Tdp | Thiamine diphosphate | Thiamine pyrophosphate | Tpp | Tryptophan catabolism
