The structure of pyruvate decarboxylase is very important in relation to its function.  It has a typical beta-alpha-beta structure,giving us parallel beta-sheets.   Pyruvate decarboxylase exists in the pyruvate dehydrogenase complex as a dimer .  These two chains are connected by the prosthetic groups thiamine pyrophosphate (TPP), where the active site lies.  It is here where the enzyme catalyzes the   decarboxylation of pyruvate, giving off carbon dioxide and transferring the hydroxyethyl group to TPP.  Beriberi, a deficiency in the uptake of vitamin B-1, which contains thiamine, results from a lack of this cofactor.

      The active site, consisting of 20 amino acids, brings the pyruvate into the core where it can react with TPP.  There are amino acids that help stabilize the reaction, primarily Glu 477 (red) and Glu 51(cyan). To get a closer look, you can zoom in by pressing this button.  The active site also consists of two more acidic amino acids, Asp 444 and Asp 28 (both orange), which contribute to active site stability.   A control mechanism of this enzyme is Cys 221 (white) and His 92 (purple), which trigger a conformational change and therefore enzyme activation or inhibition, depending on the substrate.  For example, pyruvate will trigger the activation of the enzyme, while 3-hydroxypyruvate ( a mutant) will inhibit enzyme activity.

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