Characterization of a new pantothenate kinase isoform from Helicobacter pylori.
Characterization of a new pantothenate kinase isoform from Helicobacter pylori.
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DOI：
10.1074/jbc.c500044200
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发表时间：
2005-05-27
影响因子：
4.8
通讯作者：
Strauss, E
中科院分区：
文献类型：
--
作者：
Brand, LA;Strauss, E
泛酸激酶（Pantothenate kinase, PanK）在所有生物体中催化必不可少的辅酶A （CoA）的生物合成的第一步。该酶的两种已被充分表征的同种异构体是已知的：在真细菌中占主导地位的原核PanK和主要来自哺乳动物和植物来源的真核异构体。奇怪的是，某些致病菌的基因组，包括幽门螺杆菌和铜绿假单胞菌，不包含类似于这两种异构体的PanK，尽管这些生物拥有生产辅酶a所需的所有其他生物合成机制。在这项研究中，我们克隆、过表达和鉴定了枯草芽孢杆菌及其幽门螺杆菌同源酶，并表明它们催化atp依赖性泛酸磷酸化。这些酶与任何已知的PanK不具有序列同源性，并且与细菌和真核生物的PanK异构体不同，它们的活性不受CoA或乙酰辅酶a的调节。它们也不接受泛酸抗代谢物n -戊基泛酸酰胺作为底物或被其抑制。综上所述，这些结果指出了第三种不同的PanK异构体的鉴定，这种异构体解释了幽门螺杆菌和铜绿假单胞菌等病原体中唯一已知的酶活性。
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.