The crystal structure of mouse IRG1 suggests that cis-aconitate decarboxylase has an open and closed conformation

Abstract

Itaconate, produced as an offshoot of the TCA cycle, is a multifunctional immunometabolite possessing antibacterial, antiviral, immune regulation, and tumor progression activities. The production of itaconate in biological systems is catalyzed by cis-aconitate decarboxylase (CAD, also known as immune responsive gene 1 (IRG1) in mammals). In this study, we solved the structure of IRG1 from Mus musculus (mouse IRG1). Structural comparison analysis revealed that IRG1 can exist in either an open or closed conformation and that this is controlled by the A1 loop located proximal to the active site. Our closed form structure was maintained by an unidentified molecule in the active site, which might mimic its substrate. Protein Data Bank accession codes Coordinate and structural factors were deposited with the Protein Data Bank under PDB ID: 7BR9.