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

DOI: https://doi.org/10.1039/D0MD00301H

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.



A Tandem Bioorthogonal Retro-Cope and Cope Elimination for the Activation of Covalent Inhibitors with an Acrylamide or Vinylsulfonamide Warhead in Live Cells

Yan Huang, Miao Liu, Dongguang Fan, Fan Xu, Fushuang Xiang, Qingqiang Min, and Xingyue Ji Journal of the American Chemical Society 2026 DOI:...