posted on 2001-04-21, 00:00authored byTamara A. Kale, Conrad Raab, Nathan Yu, Dennis C. Dean, Mark D. Distefano
Protein prenylation, involving the alkylation of a specific C-terminal cysteine with a C15 or C20
isoprenoid unit, is an essential posttranslational modification required by most GTP-binding proteins for normal
biological activity. Despite the ubiquitous nature of this modification and numerous efforts aimed at inhibiting
prenylating enzymes for therapeutic purposes, the function of prenylation remains unclear. To explore the role
the isoprenoid plays in mediating protein−protein recognition, we have synthesized a photoactivatable,
isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C-terminus of prenylated proteins.
Photolysis experiments with 2 and RhoGDI (GDI), a protein which interacts with prenylated Rho proteins,
suggest that the GDI is in direct contact with the isoprenoid moiety. These results, obtained using purified
GDI as well as Escherichia coli (E. coli) crude extract containing GDI, suggest that this analogue will be an
effective and versatile tool for the investigation of putative isoprenoid binding sites in a variety of systems.
Incorporation of this analogue into peptides or proteins should allow for even more specific interactions between
the photoactivatable isoprenoid and any number of isoprenoid binding proteins.