Journal
NATURE CHEMICAL BIOLOGY
Volume 5, Issue 12, Pages 920-928Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.243
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Funding
- Ministerio de Educacion y Ciencia, Spain [BFU2005-06388-C4-04-BMC, BFU2008-04188-C03-01]
- Fondo Europeo de Desarrollo Regional
- National Research Foundation, South Africa [FA2007041600013]
- Ajut de Suport a les Activitats dels Grups de Recerca [2009SGR-1091]
- Spanish Ministry of Education and Science
- National Research Foundation (South Africa) [HS2007-0022]
- Ministerio de Educacion y Ciencia (Spain)
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Unlike most other organisms, the essential five-step coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the genes encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remain unidentified. Sequence homology analyses suggest three candidates-Ykl088w, Hal3 and Vhs3-as putative PPCDC enzymes in Saccharomyces cerevisiae. Notably, Hal3 and Vhs3 have been characterized as negative regulatory subunits of the Ppz1 protein phosphatase. Here we show that YKL088w does not encode a third Ppz1 regulatory subunit, and that the essential roles of Ykl088w and the Hal3 and Vhs3 pair are complementary, cannot be interchanged and can be attributed to PPCDC-related functions. We demonstrate that while known eukaryotic PPCDCs are homotrimers, the active yeast enzyme is a heterotrimer that consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3 and Vhs3 as moonlighting proteins involved in both CoA biosynthesis and protein phosphatase regulation.
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