PhD Thesis Topic
Structure-function analysis and identification of inhibitors of protein palmitoyltransferases
Protein S-acylation commonly known as palmitoylation, is a posttranslational modification that consists in the addition of long-chain lipids on cysteine residues through a thioesther bond. This modification participates in the regulation of several processes of biological importance such as signal transduction and synaptic plasticity. A family of enzymes named Palmitoyltransferases (PATs) is responsible of almost all events of palmitoylation that have been described. PATs are polytopic membrane proteins characterized by the presence of a conserved 50 amino acid -long DHHC cysteine rich domain. There are 7 members of this family in Saccharomyces cerevisiae and 23 in humans. The information regarding these enzymes is still very scarce. Our Lab, focuses on Swf1 a PAT from S. cerevisiae involved in the S-acylation of type II transmembrane proteins, such as SNAREs and glycosyltransferases. There is growing interest in the identification of inhibitors of S-acylation, due to its role in host-cells invasion by some parasites. Additionally, PATs are involved in different types of cancers. The focus of my PhD thesis will be: 1) To continue structure-function analyses of the PAT Swf1 and complement them with structural and biochemical studies. 2) To generate assays in yeast that will enable me to isolate specific inhibitors for PATs.