Itaconate is a covalent inhibitor of the Mycobacterium tuberculosis isocitrate lyase.
Brooke X C KwaiAnnabelle J CollinsMartin J MiddleditchJonathan SperryGhader BashiriIvanhoe K H LeungPublished in: RSC medicinal chemistry (2020)
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.