Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
The Francis Crick Institute, London NW1 1AT, U.K.
Biochem J. 2018 Jun 6;475(11):1909-1937. doi: 10.1042/BCJ20180043.
In all living organisms, coenzyme A (CoA) is an essential cofactor with a unique design allowing it to function as an acyl group carrier and a carbonyl-activating group in diverse biochemical reactions. It is synthesized in a highly conserved process in prokaryotes and eukaryotes that requires pantothenic acid (vitamin B5), cysteine and ATP. CoA and its thioester derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. A novel unconventional function of CoA in redox regulation has been recently discovered in mammalian cells and termed protein CoAlation. Here, we report for the first time that protein CoAlation occurs at a background level in exponentially growing bacteria and is strongly induced in response to oxidizing agents and metabolic stress. Over 12% of gene products were shown to be CoAlated in response to diamide-induced stress CoAlation of glyceraldehyde-3-phosphate dehydrogenase was found to inhibit its enzymatic activity and to protect the catalytic cysteine 151 from overoxidation by hydrogen peroxide. These findings suggest that in exponentially growing bacteria, CoA functions to generate metabolically active thioesters, while it also has the potential to act as a low-molecular-weight antioxidant in response to oxidative and metabolic stress.
在所有生物中，辅酶 A（CoA）是一种必需的辅因子，其独特的设计使其能够在各种生化反应中作为酰基载体和羰基激活基团发挥作用。它在原核生物和真核生物中通过高度保守的过程合成，需要泛酸（维生素 B5）、半胱氨酸和 ATP。CoA 及其硫酯衍生物参与主要代谢途径、变构相互作用和基因表达的调控。最近在哺乳动物细胞中发现了 CoA 在氧化还原调节中的一种新的非传统功能，并将其命名为蛋白 CoAlation。在这里，我们首次报道在指数生长期的细菌中，蛋白 CoAlation 以背景水平发生，并强烈诱导对抗氧化剂和代谢应激的反应。超过 12%的基因产物被证明在二酰胺诱导的应激下发生 CoAlation，甘油醛-3-磷酸脱氢酶的 CoAlation 被发现抑制其酶活性，并保护催化半胱氨酸 151 不被过氧化氢过度氧化。这些发现表明，在指数生长期的细菌中，CoA 的功能是生成代谢活跃的硫酯，同时它也有可能在应对氧化和代谢应激时作为一种低分子量抗氧化剂发挥作用。
