Identification of the inhibitory mechanism of ecumicin and rufomycin 4-7 on the proteolytic activity of Mycobacterium tuberculosis ClpC1/ClpP1/ClpP2 complex.

ABSTRACT: Ecumicin and rufomycin 4-7 disrupt protein homeostasis in Mycobacterium tuberculosis by inhibiting the proteolytic activity of the ClpC1/ClpP1/ClpP2 complex. Although these compounds target ClpC1, their effects on the ATPase activity of ClpC1 and proteolytic activity of ClpC1/ClpP1/ClpP2 vary. Herein, we explored the ClpC1 molecular dynamics with these compounds through fluorescence correlation spectroscopy. The effect of these compounds on the ATPase activity of ClpC1-cys, the recombinant protein for fluorescence labeling, and proteolytic activity of ClpC1-cys/ClpP1/ClpP2 were identical to those of native ClpC1, whereas the intermolecular dynamics of fluorescence-labelled ClpC1 were different. Treatment with up to 1 nM ecumicin increased the population of slower diffused ClpC1 components

SUBMITTER: Hong J 

PROVIDER: S-EPMC9892302 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature