Substrate assisted catalysis -- application to G proteins.
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.
Kosloff
M
M
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Selinger
Z
Z
D001665:Binding Sites; D002384:Catalysis; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D009154:Mutation; D013379:Substrate Specificity
D020690:GTPase-Activating Proteins; D019204:GTP-Binding Proteins