67774 driver artpubuab oai:ddd.uab.cat:67774 doi 10.1038/nchembio.243 eng Ruiz, Amparo Universitat Autonòma de Barcelona. Departament de Bioquimica i Biologia Molecular Moonlighting Proteins Hal3 and Vhs3 Form a Heteromeric PPCDC with Ykl088w in Yeast CoA Biosynthesis Premi a l'excel·lència investigadora. 2010 Unlike 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 reservats http://www.europeana.eu/rights/rr-f/ Altres PREI 2010 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion González, Asier Universitat Autònoma de Barcelona. Institut de Biotecnologia i Biomedicina Universitat Autonòma de Barcelona. Departament de Bioquimica i Biologia Molecular Muñoz, Ivan Universitat Autonòma de Barcelona. Departament de Bioquimica i Biologia Molecular Serrano, Raquel Universitat Autonòma de Barcelona. Departament de Bioquimica i Biologia Molecular J. Albert Abrie Stellenbosch University (South Africa). Department of Biochemistry Strauss, Erick Stellenbosch University (South Africa). Department of Biochemistry Ariño Carmona, Joaquín Universitat Autonòma de Barcelona. Departament de Bioquimica i Biologia Molecular Vol. 5, Núm. 12 (2009), p. 920-928 Nature Chemical Biology 1552-4469 32 2932955 http://ddd.uab.cat/pub/artpub/2009/67774/PREI2010_natchebio.pdf Post-print 0920 928 12 5 v5n12 2009 ARTPUB UAB PREI