Enzymology and Biotechnology of Protein Prenylation
Protein prenylation is an irreversible covalent post-translational modification found in all eukaryotic cells, comprising of farnesylation and geranylgeranylation. Three prenyltransferase enzymes catalyze this modification. This three-step process increases protein hydrophobicity, and often leads to plasma membrane association. Prenylation serves as the first critical step for membrane targeting and binding, as well as mediating protein-protein interactions of a large number of Ras proteins; heterotrimeric G-proteins also require prenylation for activity.Significant interest in studying protein prenylation originally stemmed from the finding that this modification was necessary to maintain malignant activity of oncogenic Ras proteins although now it is known that prenylation is important in a wide ranges of diseases. These researchers are using computer-based methods for three subprojects within this area. They include:
- Design of caging groups used to mask the activity of substrates and inhibitors of protein prenylation
- Bioinformatic analysis of proteomic data obtained using probes that allow selective detection of prenylated proteins
- Modeling of prenyltransferase structures to design mutations that alter substrate specificity
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