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.



Discovery of the Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19

Yuto Unoh, Keiichiro Hirai, Shota Uehara, Sho Kawashima, Haruaki Nobori, Jun Satom, Hiromitsu Shibayama, Akihiro Hori, Kenji Nakahara, Kana ...