## 1 Introduction
### A Step towards Selective Inhibitors of Heterotrimeric G Proteins in Mammalian Cells  
Thirty to forty percent medical drugs are commercialized that target mammalian GPCRs. In contrast, only a few pharmacological inhibitors had been characterized that target mammalian, heterotrimeric G-proteins. However, recent studies are encouraging with respect to fundamental research on GPCR pharmacology and the potential application in GPCR-related disorders [32]. Nevertheless, only one of them has ever reached clinical trials. The first small molecules identified were bacterial toxins like CTX, _Bordella_ pertussis toxin (PTX), heat-labile enterotoxin of _Escherichia coli_, and _Pasteurella multicola_ toxin (PMT). Their mode of action is based on the chemical modification of critical residues of the G\(\alpha\)- subunit [33] with effects on GTP hydrolysis and the interacting GPCR. One of the oldest molecules that targets the G\(\alpha\)-subunit is suramin which had been originally designed for the treatment of African trypanosomiasis. The large structure of suramin prevents the association with the \(\beta\)- and X-subunits and in consequence the coupling of the GPCR [34]. In the 2000s two imidzopyrazines BIM-46174 (7-[2-amino-1-oxo-3-thio-propyl]-8-cyclohexylmethyl-2-phenyl-5,6,7,8-tetrahydro-imidazole [1,2a]-pyrazine) and BIM-46187 (85,8'S)-7,7'-[Dithiobis[(2R)-2-amino-1-oxo-3,1-propanediyil]]bis[8-(cyclohexylmethyl)-5,6,7,8-tetrahydro-2-phenyl-imidazole[1,2-alpyrazine were shown to inhibit the G\(\alpha\)s. BIM-46174 was found selectively to inhibit the cAMP increase induced by CTX via the activation of G\(\alpha\)s [35]. In addition it had anticancer activity. Interestingly, the compound had further downstream effects when it was applied in a GPCR/G protein transient expression system in cos cells [36]. Two cyclic depispeptides YM254890 and FR900359 from _Chromobacterium_ and the tropical plant _Ardisia crenata_, respectively, were selective inhibitors of the G\(\alpha\)q subunit by preventing GDP release [37]. In vivo and ex vivo studies have used FR900359 to reveal the involvement of the G\(\alpha\)q- mediated signaling pathway in various pathophysiologies including obesity and asthma [38,39]. While PTX was widely used to block G\(\alpha\)i, quinazoline derivatives have been recently demonstrated to inhibit G\(\alpha\)i selectively [40]. The G\(\beta\)X subunits are also attractive targets since they interact with multiple effectors i.e., adenylyl cyclase, phospho-inositol-3-kinase X, phospholipase C. These signaling effectors mediate key responses such as neutrophil chemotaxis and vascular cell proliferation [41,42]. The most important pharmacological tool acting on the G\(\beta\)X subunit is the GRK2 ct. The GRK2 stands for G-protein-coupled receptor kinase 2 which has the G\(\beta\)X-subunit binding domain. The GRK2 ct consists of a C-terminal 194 amino acid peptide of GRK2 responsible for the binding of the G\(\beta\)X-subunit and interfering with GRK2 activity by disrupting the membrane translocation [43] of the \(\beta\)X subunits. These findings led to the development of small molecules interfering with G\(\beta\)X association. A critical peptide SIGK was identified [44] and a potent compound M119 discovered with high apparent affinity for G\(\beta\)1\(\gamma\)2 (IC\({}_{50}\) = 200 nM). In conclusion, pharmacological inhibition of the different mammalian G\(\alpha\) or the G\(\beta\)X subunits might be a novel strategy in drug discovery since it would cause an interruption of host specific G-protein signaling which is responsible for invasion and proliferation of the parasite. Toxoplasma Gondii Uses the GPCR-Signaling Network and GTPases from the Infected Host Cell Besides Its Own Small GTPases  
_Toxoplasma gondii_ is a ubiquitous protozoan parasite found in a wide variety of hosts, including humans. It infects 30% of the human population [45]. It appears in three different forms i.e.,ocysts, tachyzoites and bradyzoites. Transmission occurs through the feces where oocysts reside.