Potential targets and inhibitors for phosphatidylserine and phosphatidylethanolamine synthesis

Potential targets and inhibitors for phosphatidylserine and phosphatidylethanolamine synthesis. (A) Potential inhibition points for the de novo pathway. The phosphatidylserine (PS) synthase from fungi (Cho1) and some bacteria (PssA) that convert cytidine diphosphate diacylglycerol (CDP-DAG) and serine (Ser) to PS would be good candidates for inhibitor development. In addition, the PS decarboxylase enzyme (PSD) that converts PS to phosphatidylethanolamine (PE), which could potentially impact parasite, fungal and select bacterial pathogens is a good point for intervention, and the compound MMV007285 has been reported to inhibit PSD activity in Plasmodium falciparum. (B) The ethanolamine kinase activity of the Plasmodium falciparum choline kinase (PfCK) in the Kennedy pathway can be inhibited by the compounds BR23 and BR25 and appears to be a good point for intervention. Red lines describe points where inhibitors have been discovered (MMV007285 and BR23 and BR25) or are lacking, but would be good points for intervention (??). Other abbreviations: Etn—ethanolamine; Etn-P—phosphoethanolamine, CDP-Etn—cytidyldiphosphate-ethanolamine.

Publication

PS, It’s Complicated: The Roles of Phosphatidylserine and Phosphatidylethanolamine in the Pathogenesis of Candida albicans and Other Microbial Pathogens. (2018) Chelsi D. Cassilly, et al. J Fungi (Basel). 2018 Mar;4(1):28. Figure: F4. Saccharomyces cerevisiae S288C

Disease mentions