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

ABSTRACT: Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be "tuned" using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the cr

SUBMITTER: Hougland JL 

PROVIDER: S-EPMC3488079 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature