1pvd
CRYSTAL STRUCTURE OF THE THIAMIN DIPHOSPHATE DEPENDENT ENZYME PYRUVATE DECARBOXYLASE FROM THE YEAST SACCHAROMYCES CEREVISIAE AT 2.3 ANGSTROMS RESOLUTIONCRYSTAL STRUCTURE OF THE THIAMIN DIPHOSPHATE DEPENDENT ENZYME PYRUVATE DECARBOXYLASE FROM THE YEAST SACCHAROMYCES CEREVISIAE AT 2.3 ANGSTROMS RESOLUTION
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 crystal structure of pyruvate decarboxylase (EC 4.1.1.1), a thiamin diphosphate-dependent enzyme isolated from Saccharomyces cerevisiae, has been determined and refined to a resolution of 2.3 A. Pyruvate decarboxylase is a homotetrameric enzyme which crystallizes with two subunits in an asymmetric unit. The structure has been refined by a combination of simulated annealing and restrained least squares to an R factor of 0.165 for 46,787 reflections. As in the corresponding enzyme from Saccharomyces uvarum, the homotetrameric holoenzyme assembly has approximate 222 symmetry. In addition to providing more accurate atomic parameters and certainty in the sequence assignments, the high resolution and extensive refinement resulted in the identification of several tightly bound water molecules in key structural positions. These water molecules have low temperature factors and make several hydrogen bonds with protein residues. There are six such water molecules in each cofactor binding site, and one of them is involved in coordination with the required magnesium ion. Another may be involved in the catalytic reaction mechanism. The refined model includes 1074 amino acid residues (two subunits), two thiamin diphosphate cofactors, two magnesium ions associated with cofactor binding and 440 water molecules. From the refined model we conclude that the resting state of the enzyme-cofactor complex is such that the cofactor is already deprotonated at the N4' position of the pyrimidine ring, and is poised to accept a proton from the C2 position of the thiazolium ring. Crystal structure of the thiamin diphosphate-dependent enzyme pyruvate decarboxylase from the yeast Saccharomyces cerevisiae at 2.3 A resolution.,Arjunan P, Umland T, Dyda F, Swaminathan S, Furey W, Sax M, Farrenkopf B, Gao Y, Zhang D, Jordan F J Mol Biol. 1996 Mar 1;256(3):590-600. PMID:8604141[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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