Figure 1

The yeast PPCDC enzyme and its constituent proteins.

(a) Schematic representation of the active PPCDC in yeast, its constituent components and the various questions surrounding their respective interactions. The heterotrimeric PPCDC is formed by the combination of Hal3 and/or Vhs3 (which contributes the catalytically essential His residue, shown in blue) with Cab3 (which contributes the catalytically essential Cys residue, shown in orange) to give a complex with a single functional active site. Note that although Cab3 also has a His residue (shown in grey), it has been shown to be non-functional⁵. In addition, both Hal3 and Vhs3 also exist as homomeric trimers and act as inhibitors of the protein phosphatase Ppz1 (shown in orange). Characterizing the interchange of monomers between the homo- and heterotrimers and the nature of the inhibitory interaction with Ppz1 is the focus of this study. (b) The reaction catalysed by PPCDC enzymes (in grey box) with its two-step mechanism shown on the right. Note that the catalytically essential His residue is important for the first step (the oxidative decarboxylation), while the Cys is required for the reduction of the enethiol intermediate (the second step). (c) Schematic alignment of the PDs of Hal3, Vhs3 and Cab3 with human PPCDC (HsCoaC). The non-homologous insertion regions of Hal3^PD and Vhs3^PD are represented in white, while the catalytically essential His (in HsCoaC, Hal3^PD and Vhs3^PD) and Cys (in HsCoaC and Cab3^PD) residues are indicated in blue and orange respectively. The non-functional His residue in Cab3^PD is denoted in grey.