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.



Morita–Baylis–Hillman Adduct Chemistry as a Tool for the Design of Lysine-Targeted Covalent Ligands

Marco Paolino, Giusy Tassone, Paolo Governa, Mario Saletti, Matteo Lami, Riccardo Carletti, Filippo Sacchetta, Cecilia Pozzi, Maurizio Orlan...