GTPgammaS

GTPgammaS (GTPγS, guanosine 5'-O-[gamma-thio]triphosphate) is a non-hydrolyzable or slowly hydrolyzable G-protein-activating analog of guanosine triphosphate (GTP). Many GTP binding proteins demonstrate activity when bound to GTP, and are inactivated via the hydrolysis of the phosphoanhydride bond that links the γ-phosphate to the remainder of the nucleotide, leaving a bound guanosine diphosphate (GDP) and releasing an inorganic phosphate. This usually occurs rapidly, and the GTP-binding protein can then only be activated by exchanging the GDP for a new GTP molecule.[1] The substitution of sulfur for one of the oxygens of the γ-phosphate of GTP creates a nucleotide that either cannot be hydrolyzed or is only slowly hydrolyzed. This prevents the GTP-binding proteins from being inactivated, and allows the cellular processes that they carry out when active to be more easily studied.[2]

GTPgammaS
Names
IUPAC name
[(2S,3R,4S,5S)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphinothioyl hydrogen phosphate
Identifiers
3D model (JSmol)
  • InChI=34654
    Key: XOFLBQFBSOEHOG-UUOKFMHZBU
  • InChI=1/C10H16N5O13P3S/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(26-9)1-25-29(19,20)27-30(21,22)28-31(23,24)32/h2-3,5-6,9,16-17H,1H2,(H,19,20)(H,21,22)(H2,23,24,32)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
  • S=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n1cnc2c1NC(=N/C2=O)\N)[C@H](O)[C@@H]3O
Properties
C10H16N5O13P3S
Molar mass 539.24 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

The consequences of the constitutive activation of GTP-binding proteins include stimulation of phosphoinositide hydrolysis,[3] cyclic AMP accumulation or elimination,[4] and activation of specific proto-oncogenes.[5] The 35S labelled radioligand of the compound, 35SGTPγS, is used in autoradiography and G-protein binding studies.[6]

References
  1. Harrison C, Traynor JR (December 12, 2003). "The [35S]GTPγS binding assay: approaches and applications in pharmacology". Life Sciences. 74 (4): 489–508. doi:10.1016/j.lfs.2003.07.005. PMID 14609727. Retrieved April 26, 2021.
  2. Spoerner M, Nuehs A, Herrmann C, Steiner G, Kalbitzer HR (March 2007). "Slow conformational dynamics of the guanine nucleotide‐binding protein Ras complexed with the GTP analogue GTPγS". The FEBS Journal. 274 (6): 1419–1433. doi:10.1111/j.1742-4658.2007.05681.x. PMID 17302736.
  3. White HL, Scates PW (1991). "Effects of GTPγS and other nucleotides on phosphoinositide metabolism in crude rat brain synaptosomal preparations". Neurochemistry International. 18 (3): 381–387. doi:10.1016/0197-0186(91)90170-I. PMID 20504715. S2CID 44683770. Retrieved April 26, 2021.
  4. Baker SP, Scammells PJ, Belardinelli L (July 2000). "Differential A1-adenosine receptor reserve for inhibition of cyclic AMP accumulation and G-protein activation in DDT1 MF-2 cells". British Journal of Pharmacology. 130 (5): 1156–1164. doi:10.1038/sj.bjp.0703405. PMC 1572163. PMID 10882402.
  5. Pennington SR, Hesketh TR, Metcalfe JC (January 25, 1988). "GTPγS activation of proto-oncogene expression in transiently permeabilised Swiss 3T3 fibroblasts". FEBS Letters. 227 (2): 203–208. doi:10.1016/0014-5793(88)80899-8. PMID 3276558.
  6. Strange PG (November 2010). "Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors". British Journal of Pharmacology. 161 (6): 1238–1249. doi:10.1111/j.1476-5381.2010.00963.x. PMC 3000650. PMID 20662841.


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