Molecular cloning of CoA synthase - The missing link in CoA biosynthesis

Zhyvoloup, A, Nemazanyy, I, Babich, A, Panasyuk, G, Pobigailo, N, Vudmaska, M, Naidenov, V, Kukharenko, O, Palchevskii, S, Savinska, L, and others. (2002) Molecular cloning of CoA synthase - The missing link in CoA biosynthesis. Journal of Biological Chemistry, 277 (25). 22107 - 22110. ISSN 0021-9258. (doi:10.1074/jbc.C200195200) (KAR id:61529)

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Official URL: http://dx.doi.org/10.1074/jbc.C200195200

Abstract

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 similar to60 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.

Item Type:	Article
DOI/Identification number:	10.1074/jbc.C200195200
Uncontrolled keywords:	PANTOTHENATE KINASE GENE, COENZYME-A METABOLISM, ESCHERICHIA-COLI, RAT-LIVER, ADENYLYLTRANSFERASE, HEART, PURIFICATION, COMPLEX, MUSCLE, STATE
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Depositing User:	Tim Fenton
Date Deposited:	19 Dec 2018 06:35 UTC
Last Modified:	05 Nov 2024 10:55 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/61529 (The current URI for this page, for reference purposes)

University of Kent Author Information

Fenton, TR.

Creator's ORCID:	https://orcid.org/0000-0002-4737-8233
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