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Originally published In Press as doi:10.1074/jbc.C500044200 on March 28, 2005

J. Biol. Chem., Vol. 280, Issue 21, 20185-20188, May 27, 2005
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Characterization of a New Pantothenate Kinase Isoform from Helicobacter pylori*{boxs}

Leisl A. Brand and Erick Strauss{ddagger}

From the Department of Chemistry, Stellenbosch University, Matieland 7602, South Africa

Pantothenate kinase (PanK) catalyzes the first step in the biosynthesis of the essential and ubiquitous cofactor coenzyme A (CoA) in all organisms. Two well characterized isoforms of the enzyme are known: a prokaryotic PanK that predominates in eubacteria and a eukaryotic isoform that has primarily been characterized from mammalian and plant sources. Curiously, the genomes of certain pathogenic bacteria, including Helicobacter pylori and Pseudomonas aeruginosa, do not contain a PanK similar to either isoform, although these organisms possess all the other biosynthetic machinery required for CoA production. In this study we cloned, overexpressed and characterized an enzyme from Bacillus subtilis and its homologue from H. pylori and show that they catalyze the ATP-dependent phosphorylation of pantothenate. These enzymes do not share sequence homology with any known PanK, and unlike the bacterial and eukaryotic PanK isoforms their activity is not regulated by either CoA or acetyl-CoA. They also do not accept the pantothenic acid antimetabolite N-pentylpantothenamide as a substrate or are inhibited by it. Taken together, these results point to the identification of a third distinct isoform of PanK that accounts for the only known activity of the enzyme in pathogens such as H. pylori and P. aeruginosa.


Received for publication, January 31, 2005 , and in revised form, March 9, 2005.

* This work was supported by grants from the National Research Foundation of South Africa (GUN 2054218) and from Stellenbosch University. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1 and supplemental Table I.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY912104.

{ddagger} To whom correspondence should be addressed: Dept. of Chemistry, Private Bag X1, Stellenbosch University, Matieland 7602, South Africa. Tel.: 27-21-808-3355; Fax: 27-21-808-3360; E-mail: estrauss{at}sun.ac.za.


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