Antibacterial ADP-ribosyl cyclase toxins inhibit bacterial growth by rapidly depleting NAD(P)^.

ABSTRACT: In metazoans, enzymes belonging to the bifunctional ADP-ribosyl cyclase/cyclic ADP-ribose (cADPr) hydrolase family regulate diverse cellular processes by synthesizing and hydrolyzing the intracellular second messenger cADPr, derived from the electron carrier NAD⁺. However, bacterial enzymes belonging to this family have not been characterized. Here, we identify a bacterial ADP-ribosyl cyclase that is associated with the type VII secretion system and functions as an antibacterial toxin. This enzyme, which we name Tac1, inhibits bacterial growth by rapidly hydrolyzing NAD⁺ and NADP⁺. We determine the X-ray crystal structure of Tac1 to a resolution of 1.4 Å, which reveals that this protein adopts the core catalytic fold of metazoan ADP-ribosyl cyclase enzymes

SUBMITTER: Colautti J 

PROVIDER: S-EPMC12356396 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature