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Publication : Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis.

First Author  Zhyvoloup A Year  2002
Journal  J Biol Chem Volume  277
Issue  25 Pages  22107-10
PubMed ID  11980892 Mgi Jnum  J:77231
Mgi Id  MGI:2181228 Doi  10.1074/jbc.C200195200
Citation  Zhyvoloup A, et al. (2002) Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis. J Biol Chem 277(25):22107-10
abstractText  Coenzyme A functions as a carrier of acetyl and acyl groups in living cells and is essential for numerous biosynthetic, energy-yielding, and degradative metabolic pathways. There are five enzymatic steps in CoA biosynthesis. To date, molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals has been only reported for pantothenate kinase. In this study, we present cDNA cloning and functional characterization of CoA synthase. It has an open reading frame of 563 aa and encodes a protein of approximately 60 kDa. Sequence alignments suggested that the protein possesses both phosphopantetheine adenylyltransferase and dephospho-CoA kinase domains. Biochemical assays using wild type recombinant protein confirmed the gene product indeed contained both these enzymatic activities. The presence of intrinsic phosphopantetheine adenylyltransferase activity was further confirmed by site-directed mutagenesis. Therefore, this study describes the first cloning and characterization of a mammalian CoA synthase and confirms this is a bifunctional enzyme containing the last two components of CoA biosynthesis.
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