67774artpubuabdriveroai:ddd.uab.cat:67774doi10.1038/nchembio.243engRuiz, AmparoUniversitat Autonòma de Barcelona. Departament de Bioquimica i Biologia MolecularMoonlighting Proteins Hal3 and Vhs3 Form a Heteromeric PPCDC with Ykl088w in Yeast CoA BiosynthesisPremi a l'excel·lència investigadora. 2010Unlike most other organisms, the essential five-step Coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the gene(s) encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remains unidentified. Sequence homology analyses suggest three candidates, namely Ykl088w, Hal3 and Vhs3, as putative PPCDC enzymes in Saccharomyces cerevisiae. Interestingly, 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/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 which consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3/Vhs3 as moonlighting proteins, involved in both CoA biosynthesis and protein phosphatase regulation.Tots els drets reservatshttp://www.europeana.eu/rights/rr-f/AltresPREI 2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionGonzález, AsierUniversitat Autonòma de Barcelona. Departament de Bioquimica i Biologia MolecularUniversitat Autònoma de Barcelona. Institut de Biotecnologia i BiomedicinaMuñoz, IvanUniversitat Autonòma de Barcelona. Departament de Bioquimica i Biologia MolecularSerrano, RaquelUniversitat Autonòma de Barcelona. Departament de Bioquimica i Biologia MolecularJ. Albert AbrieStellenbosch University (South Africa). Department of BiochemistryStrauss, ErickStellenbosch University (South Africa). Department of BiochemistryAriño Carmona, JoaquínUniversitat Autonòma de Barcelona. Departament de Bioquimica i Biologia MolecularVol. 5, Núm. 12 (2009), p. 920-928Nature Chemical Biology1552-4469322932955http://ddd.uab.cat/pub/artpub/2009/67774/PREI2010_natchebio.pdfPost-print0920928125v5n122009ARTPUBPREIUABfile0MD5159abb990a673141eace22971cf2d56a2932955bytestream1.6filepathpub/artpub/2009/67774/PREI2010_natchebio.pdfdisk