Emerging Concepts on the Role of ADP-Ribosylation

Abstract

NAD + has emerged as a crucial element in both bioenergetic and signaling pathways, since it acts as a key regulator of cellular and organism homeostasis. NAD + is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, and a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD + to remove acetyl groups from proteins. NAD + is also a precursor of cyclic ADP-ribose, a second messenger in the release and signaling of Ca ++ , and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2 -5 A)-two immune response-activating compounds. In the biological systems considered in this review, NAD + is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review, the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, ADP-ribosylating enzymes are introduced, as well as the importance to restore the NAD + pools in these systems. Finally, a special attention is presently focused on viral macrodomains, aimed to develop inhibitors to improve the immune response to viruses.

Inhibition of Viral Macrodomain of COVID-19 and Human TRPM2 by losartan

“…ADPR-binding to the CoVs nsp3 macrodomain that is necessary for the initiation of virus replication, whereas the hydrolase activity facilitates to amplify the replication complex. Therefore, macrodomains can remove ADP-ribosy polymer from modified proteins (7).…”