Cromolyn as a novel pharmacophore of the Zα domain of the RNA-editing enzyme ADAR1p150.

ABSTRACT: ADAR1p150 is a critical RNA-editing enzyme for maintaining cellular homeostasis through dsRNA binding, protein-protein interactions, and adenosine-to-inosine (A-to-I) editing. Beyond its dsRNA binding domains, ADAR1p150 contains a Zα domain that can induce a conformational switch of dsDNA and dsRNA from stable B/A forms to a higher-energy left-handed Z form. By stabilizing Z-RNA, ADAR1p150 is thought to modulate immune activation by competing with dsRNA sensors like MDA5 and ZBP1. ADAR1p150's editing activity minimizes dsRNA's presence and prevents dsRNA-mediated inflammatory pathways' activation. Our study employs NMR to introduce a novel pharmacophore model for Zα domain binders. We identify cromoglicic acid, also known as the FDA-approved drug cromolyn, as an ADAR1 Zα binder that compet

SUBMITTER: Langdon N 

PROVIDER: S-EPMC12514971 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature