Itaconate is a covalent inhibitor of the Mycobacterium tuberculosis isocitrate lyase
Brooke XC Kwai, Annabelle J Collins, Martin J Middleditch, Jonathan Sperry, Ghader Bashiri, Ivanhoe KH Leung
RSC MEDICINAL CHEMISTRY | ROYAL SOC CHEMISTRY | Published : 2021
Itaconate is a mammalian antimicrobial metabolite that inhibits the isocitrate lyases (ICLs) of Mycobacterium 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.