Widespread deployment of the human CD38 ADP-ribosyl cyclase fold in antibacterial and anti-eukaryotic polymorphic toxins.

ABSTRACT: Bacterial polymorphic toxins are modular weapons that mediate intermicrobial competition and host interactions by delivering diverse cytotoxic domains through specialized secretion systems. Here, we identify and characterize a novel toxin domain in Pantoea ananatis that displays remarkable structural and functional conservation with the human enzyme CD38. This bacterial toxin, fused to a type VI secretion system (T6SS) PAAR domain, harbors a C-terminal ADP-ribosyl cyclase (ARC) domain that hydrolyzes NAD⁺ and NADP⁺in vitro and in vivo, leading to growth inhibition in both bacterial and eukaryotic cells. The 1.6-Å resolution structure of ARC reveals that it adopts a globular fold nearly identical to the human CD38 ADP-ribosyl cyclase, with key catalytic residues conser

SUBMITTER: Martinkus J 

PROVIDER: S-EPMC12605009 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature