Guanosine 5’-[γ-thio]triphosphate (GTPγS) is a hydrolysis-resistant analog of GTP that binds to and activates G proteins in the presence of magnesium.1 GTPγS has been used to obtain crystal structures of GTPases in their active states, as well as measure the stability of GTPases in the presence of ligands.2,3 A radiolabeled form of GTPγS, [35S]GTPγS, is commonly used in binding assays to determine agonism or antagonism at G protein-coupled receptors (GPCRs).1,4
1.Harrison, C., and Traynor, J.R.The [35S]GTPγS binding assay: Approaches and applications in pharmacologyLife Sci.74(4)489-508(2003) 2.Ihara, K., Muraguchi, S., Kato, M., et al.Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogueJ. Biol. Chem.273(16)9656-9666(1998) 3.Lito, P., Solomon, M., Li, L.-S., et al.Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanismScience351(6273)604-608(2016) 4.Strange, P.G.Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptorsBr. J. Pharmacol.161(6)1238-1249(2010)