Kumar Parimal, Chhibber Manmohan, Surolia Avadhesha
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Biochem Biophys Res Commun. 2007 Oct 5;361(4):903-9. doi: 10.1016/j.bbrc.2007.07.080. Epub 2007 Jul 27.
Coenzyme A is an indispensable cofactor for all organisms and holds a central position in a number of pathways. Prokaryotic enzymes involved in the synthesis of CoA are quite different from their mammalian counterparts; hence, they are good targets for the development of antimicrobials to treat many diseases. There are antimicrobials that act by inhibiting CoA biosynthesis. It has been suggested that pantothenol exhibits antibacterial activity by competitively inhibiting pantothenate kinase, a key regulatory enzyme for CoA synthesis. Contrary to these suggestions, in this paper, we demonstrate that pantothenol acts as a substrate for Mycobacterium tuberculosis and Escherichia coli pantothenate kinases. The product, 4'-phosphopantothenol, thus formed inhibits competitively the utilization of 4'-phosphopantothenate by CoaBC. Thus, it is the failure of CoaBC to utilize 4'-phosphopantothenol as a substrate that accounts for the bactericidal activity of pantothenol.
辅酶A是所有生物体不可或缺的辅助因子，在许多代谢途径中占据核心地位。参与辅酶A合成的原核生物酶与哺乳动物的同类酶有很大不同；因此，它们是开发治疗多种疾病的抗菌药物的理想靶点。有一些抗菌药物通过抑制辅酶A生物合成发挥作用。有人提出泛醇通过竞争性抑制泛酸激酶（辅酶A合成的关键调节酶）表现出抗菌活性。与这些观点相反，在本文中，我们证明泛醇是结核分枝杆菌和大肠杆菌泛酸激酶的底物。由此形成的产物4'-磷酸泛醇竞争性抑制CoaBC对4'-磷酸泛酸的利用。因此，CoaBC无法将4'-磷酸泛醇用作底物导致了泛醇的杀菌活性。
