GTPases comprise a diverse family of enzymes that participate in a variety of cellular processes including signal transduction, protein synthesis, and intracellular transport. GTPases typically participate in these processes as binary switches; activating a process in the GTP-bound state and inactivating a process in the GDP bound state. Importantly, the deregulation of the GTP/GDP cycle for a number of GTPases are known to be associated with cancers.
ActivX has developed a desthiobiotin acyl phosphate GTP probe that covalently modifies GTPases in the active site. Profiling numerous proteomes has lead to identification of members from most sub-families of GTPases, suggesting that the probe could be a useful tool for profiling the distribution of GTPases.
The primary labeling site of the GTP probe is in the phosphate binding region of GTPases. For some GTPases, probe-labeling at this site is sensitive to EDTA-dependent nucleotide exchange, raising the possibility that the GTP probe could be used to monitor the activity of GTPases in proteomes.