Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme.

摘要: The separate catalytic roles of Zn2+ and Mg2+ the specificity prenyl pyrophosphate-binding site rat brain protein farnesyltransferase were explored using a purified enzyme preparation. binding p21Hras to was abolished by dialysis against EDTA restored addition ZnCl2, as demonstrated chemical cross-linking. other substrate, farnesyl pyrophosphate, independent divalent cations, gel filtration. Transfer enzyme-bound group bound required Mg2+. Geranylgeranyl pyrophosphate with an affinity equal that but geranylgeranyl not transferred efficiently p21Hras. It also modified containing COOH-terminal leucine, shown previously be good substrate for geranylgeranyltransferase. We conclude is metalloenzyme most likely contains at peptide-binding site. thus resembles certain metallopeptidases, including carboxypeptidase A angiotensin-converting enzyme. Strategies developed screen inhibitors those enzymes may aid in search farnesyltransferase.