Nematode phospholipid metabolism: an example of closing the genome-structure-function circle.

Parasitic nematodes that infect humans, animals, and plants cause health problems, livestock and agricultural losses, and economic damage worldwide and are important targets for drug development. The growing availability of nematode genomes supports the discovery of new pathways that differ from host organisms and are a starting point for structural and functional studies of novel antiparasitic targets. As an example of how genome data, structural biology, and biochemistry integrate into a research cycle targeting parasites, we summarize the discovery of the phosphobase methylation pathway for phospholipid synthesis in nematodes and compare the phosphoethanolamine methyltransferases (PMTs) from nematodes, plants, and Plasmodium. Crystallographic and biochemical studies of the PMTs in this pathway provide a foundation that guides the next steps that close the genome-structure-function circle.