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.¹GTPγS 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.^2,3A 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)