The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative rate-limiting step for the GTPase reaction and shown that GTPase-deficient oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs could potentially be designed to restore the blocked GTPase reaction.
Bibliographical noteFunding Information:
We thank R. Kornberg for stimulating discussion, and M. Schramm and D. Cassel for helpful comments. Our research was supported by grants from the Israeli Science Foundation (ISF), the National Institute of Health (EY 03529) and the Minerva Foundation.
ASJC Scopus subject areas
- Molecular Biology