Expansion of protein farnesyltransferase specificity using "tunable" active site interactions: Development of bioengineered prenylation pathways

Background: FTase recognizes and modifies many proteins with C-terminal CA₁A₂X sequences. Results: Mutating active site residues Trp-102β and Trp-106β significantly alters FTase peptide selectivity both in vitro and in vivo. Conclusion: FTase substrate selectivity includes negative discrimination that can be relaxed/altered without losing activity. Significance: Deciphering FTase peptide recognition allows creation of bioengineered prenylation pathways and provides a model for other multispecific enzymes.