GTP shift

FIGURE 4.19 Correlation of the GTP shift for P-adrenoceptor agonists in turkey erythocytes (ordinates) and intrinsic activity of the agonists in functional studies (abscissae). Data redrawn from [16]. 

We observed that GTP shifts the Tetrahymena pre-RNA to a conformation that migrates just a bit more slowly than the native pre-RNA (Emerick etal, 1996 Pan etal, 1999). Only the native form of the RNA was affected ... 

These compounds and the 5 -deoxy analogues of CPA and R-PIA (obtained as gifts) together with three reference compounds were tested in vitro for their affinity for the adenosine A, and Aja receptors, and their GTP shift on the A receptors (Table 2). 

Adenosine Ai (Kj-values in presence and absence of GTP and GTP shifts) and Aj receptor affinities of the N -substituted deoxy analogues. 

The in vivo potencies (ECjo.u) of the compounds correlated well with their apparent adenosine A, receptor affinities as determined in the absence of GTP (Table 2). With respect to intrinsic activity a fair correlation between relative GTP shifts and E values was observed. The 2 - and 3 -deoxy analogues of CPA proved partial agonists in vitro and in vivo. 

One should note overall, that while some of these suggested mechanisms may in the future prove to have a role in the control of smooth muscle contraction, in chemically skinned preparations maximum force development follows activation by the MLCK active subunit in extremely low Ca " ion concentrations. The conclusion can hardly be avoided that phosphorylation alone is sufficient for activation, and if another mechanism is involved, it is not necessary for the initial genesis of force. If such mechanisms are operative, then they might be expected to run in parallel or consequent to myosin phosphorylation. A possible example of this category of effect is that a GTP-dependent process (G-protein) shifts the force vs. Ca ion concentration relationship to lower Ca ion concentrations. This kind of mechanism calls attention to the divergence of signals along the intracellular control pathways. 

The reaction equilibrium is shifted to the right. The major supplier of phosphate groups is GTP, but for this purpose, ATP may also be available. 

Ras, a historical proto-oncogene, is frequently mutated in many human cancers, including 90% of pancreatic cancers, 50% of colorectal cancers, 30% of lung cancers, and 15-30% of melanomas [10-12]. There are three Ras genes that encode four family members K-Ras (two alternatively spliced isoforms), H-Ras, and N-Ras. Mutations are most commonly found in K-Ras [13]. These mutations result in impaired GTP hydrolysis, which shifts the equilibrium toward GTP-bound active Ras, and results in constitutive intracellular signaling. 

Elongation Step 3 Translocation In the final step of the elongation cycle, translocation, the ribosome moves one codon toward the 3 end of the mRNA (Fig. 27-25a). This movement shifts the anticodon of the dipeptidyl-tRNA, which is still attached to the second codon of the mRNA, from the A site to the P site, and shifts the de-acylated tRNA from the P site to the E site, from where the tRNA is released into the cytosol. The third codon of the mRNA now lies in the A site and the second codon in the P site. Movement of the ribosome along the mRNA requires EF-G (also known as translocase) and the energy provided by hydrolysis of another molecule of GTP. 

Allin, C., and Gerwert, K. (2001). Ras catalyzes GTP hydrolysis by shifting negative charges from y- to //-phosphate as revealed by time-resolved FTIR difference spectroscopy. Biochemistry 40, 3037-3046. 

Quirk s argument is strengthened by Muller s finding that increasing the concentration of silyl ketene acetal retards GTP the result of shifting the equilibrium between enolate and complex to the complex side and thus lowering the concentration of bare enolate and the rate of polymerization [24] (Scheme 13). 

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