Structure and catalytic mechanism of methylisocitrate lyase, a potential drug target against Coxiella burnetii.

ABSTRACT: We present a comprehensive investigation into the catalytic mechanism of methylisocitrate lyase, a potential drug target candidate against the zoonotic pathogen Coxiella burnetii, the causative agent of Q fever and a federal select agent. Current treatment regimens are prolonged, often with incomplete clearance of the pathogen. We utilized a structure-based bioinformatics pipeline to identify methylisocitrate lyase as a candidate therapeutic target against C. burnetii from a list of essential genes. WT C. burnetii methylisocitrate lyase has a k_cat of 13.8 s^-1 (compared to 105 s^-1 for Salmonella enterica), and isocitrate inhibits with a K_I of 11 mM. We have determined the previously uncharacterized substrate-bound structure of this enzyme family,

SUBMITTER: Stuart WS 

PROVIDER: S-EPMC12145553 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature