Saturday, October 24, 2020

Itaconate is a covalent inhibitor of the Mycobacterium tuberculosis isocitrate lyase

Brooke X. C. Kwai, Annabelle J. Collins, Martin J. Middleditch, Jonathan Sperry,   Ghader Bashiri and  Ivanhoe K. H. Leung 

RSC Med. Chem., 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.

Covalent drug discovery using sulfur(VI) fluoride exchange warheads

Huang Huang, Lyn H. Jones Expert Opinion on Drug Discovery , 2023 Covalent drug discovery has ...