GDP hydrolysis

G-proteins exist either in an active or an inactive state, depending on the guanylate nucleotide that is bound. In the inactive state, G-protein binds to GDP. In the active state, GTP is bound to the G-pro-tein. G-proteins have an intrinsic GTPase activity, which converts bound GTP to GDP. Hydrolysis of GTP by the G-protein converts the G-protein back to an inactive state. Thus the cycle of the G-protein is as follows ... 

Binding to Gpy locks the flexible switch regions I and II of Ga into a conformation that firmly binds GDP but is nonproductive for GTP binding and hydrolysis. The replacement of GDP with GTP causes local but dramatic conformational changes to switch regions I and 11, as shown in the Go GTP-yS structure, which disrupt nearly all of the contacts between Gp. and Ga in the switch interface, thereby triggering release of Ga from Gpy (see Figures 13.10 and 13.11). 

Berghuis, A.M., et al. Structure of the GDP-Pi complex of Gly203-Ala Giai a mimic of the ternary product complex of Ga-catalyzed GTP hydrolysis. Structure 4 1277-1290, 1996. 

The charging of the tRNA molecule with the aminoacyl moiety requires the hydrolysis of an ATP to an AMP, equivalent to the hydrolysis of two ATPs to two ADPs and phosphates. The entry of the aminoacyl-tRNA into the A site results in the hydrolysis of one GTP to GDP. Translocation of the newly formed pep-tidyl-tRNA in the A site into the P site by EF2 similarly results in hydrolysis of GTP to GDP and phosphate. Thus, the energy requirements for the formation of one peptide bond include the equivalent of the hydrolysis of two ATP molecules to ADP and of two GTP molecules to GDP, or the hydrolysis of four high-energy phosphate bonds. A eukaryotic ribosome can incorporate as many as six amino acids per second prokaryotic ribosomes incorporate as many as 18 per second. Thus, the process of peptide synthesis occurs with great speed and accuracy until a termination codon is reached. 

The ttj protein has inttinsic GTPase activity. The active fotm, (Xs GTP, is inactivated upon hydrolysis of the GTP to GDP the ttimetic G complex (apy) is then te-fotmed and is ready fot anothet cycle of activation. Gholeta and pettussis toxins catalyze the ADP-tibosylation of OL, and aj.2 (see Table 43-3), tespec-... 

COPI vesicle budding is triggered by the hydrolysis of GTP to GDP by membrane-associated ARFl. Once in the membranes, ARF-GTP recruits pre-assembled coatomers, resulting in membrane deformation. The cytoplasmic tail of an abundant transmembrane protein, known as p24,... 

Ran (the Ras-related nuclear protein) is the major regulator of nucleo-cytoplas-mic transport [134] across the nuclear pore complex (NPC). Like other small Ras-like GTP-binding proteins, it switches between a GTP- and a GDP-bound form by GTP-hydrolysis and nucleotide exchange [135]. In contrast to its relatives, Ran does not undergo posttranslational modification. 

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