Itaconate is a covalent inhibitor of theMycobacterium tuberculosisisocitrate lyase

Abstract

Itaconate is a mammalian antimicrobial metabolite that inhibits the isocitrate lyases (ICLs) ofMycobacterium tuberculosis. Herein, we report that ICLs form a covalent adduct with itaconate through their catalytic cysteine residue. These results reveal atomic details of itaconate inhibition and provide insights into the catalytic mechanism of ICLs.