Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani.

ABSTRACT: We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical

SUBMITTER: Prasad SR 

PROVIDER: S-EPMC9525708 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature