GTP

The ACES II program of Professor Rod Bartlett webpage http //www.gtp.ufl.edu/Aces2/... 

A vital biophysico-chemical problem is to understand how chemical energy (released by ATP or GTP hydrolysis... 

In order to further cla.ssify these reactions, a search for reactions that transform ATP to ADP was made, resulting in 139 reactions 139 of the above 304 reactions involve the breaking of a P-0 bond in ATP, emphasizing the central importance of this bond breaking as a source of energy, An additional three reactions involve the transformation of GTP to GDP. As many reactions transferring a phosphate group... 

Section 28 14 The nucleotide sequence of DNA can be determined by a technique m which a short section of single stranded DNA is allowed to produce its complement m the presence of dideoxy analogs of ATP TTP GTP and CTP DNA formation terminates when a dideoxy analog is incorporated into the growing polynucleotide chain A mixture of polynucleotides dif fermg from one another by an incremental nucleoside is produced and analyzed by electrophoresis From the observed sequence of the comple mentary chain the sequence of the original DNA is deduced... 

The anionic polymerization of methacrylates using a silyl ketene acetal initiator has been termed group-transfer polymerization (GTP). First reported by Du Pont researchers in 1983 (100), group-transfer polymerization allows the control of methacrylate molecular stmcture typical of living polymers, but can be conveniendy mn at room temperature and above. The use of GTP to prepare block polymers, comb-graft polymers, loop polymers, star polymers, and functional polymers has been reported (100,101). 

G-Protein Coupling. The heterotrimeric guanosine triphosphate (GTP) binding proteins, known as G-proteins, are a principal family of proteins serving to couple membrane receptors of the G-protein family to ionic and biochemical processes. This topic is reviewed in References 63—67. 

Fig. 10. The receptor—G-protein sequence. An activated receptor interacts with the trimeric GDP-ligated receptor to cause an interchange of GDP by GTP and dissociation into the activated Ga—GTP (left) and G y (right) subunits. These then interact with a variety of effectors. The purpose of the activated...

A critical component of the G-protein effector cascade is the hydrolysis of GTP by the activated a-subunit (GTPase). This provides not only a component of the amplification process of the G-protein cascade (63) but also serves to provide further measures of dmg efficacy. Additionally, the scheme of Figure 10 indicates that the coupling process also depends on the stoichiometry of receptors and G-proteins. A reduction in receptor number should diminish the efficacy of coupling and thus reduce dmg efficacy. This is seen in Figure 11, which indicates that the abiUty of the muscarinic dmg carbachol [51 -83-2] to inhibit cAMP formation and to stimulate inositol triphosphate, IP, formation yields different dose—response curves, and that after receptor removal by irreversible alkylation, carbachol becomes a partial agonist (68). 

Folic acid is synthesized both in microorganisms and in plants. Guanosine-5-ttiphosphate (GTP) (33), -aminobenzoic acid (PABA), and L-glutamic acid are the precursors. Reviews are available for details (63,64). The sequence of reactions responsible for the enzymatic conversion of GTP to 7,8-dihydrofohc acid (2) is shown. 

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. 

These organisms have been used frequently in the elucidation of the biosynthetic pathway (37,38). The mechanism of riboflavin biosynthesis has formally been deduced from data derived from several experiments involving a variety of organisms (Fig. 5). Included are conversion of a purine such as guanosine triphosphate (GTP) to 6,7-dimethyl-8-D-ribityUuma2ine (16) (39), and the conversion of (16) to (1). This concept of the biochemical formation of riboflavin was verified in vitro under nonen2ymatic conditions (40) (see Microbial transformations). 

The nucleotide form of ribavirin does not manifest its antiviral activity simply by lowering the GTP levels, but may indeed participate directly in binding to specific G proteins (124). Ribavirin has recently been studied as an inhibitor of vesicular stomatitis vims and La Crosse vims (125). Of the phosphorylated forms of the dmg, ribavirin-5 -diphosphate was by far the most potent inhibitor of viral repHcation for these two vimses. 

This interesting conversion of a five- into a six-membered heterocyclic ring was proven by the isolation of the enzyme GTP-cyclohydrolase from E. coli (71MI21600) and a similar one from Lactobacillus platarum (B-71MI21601) which catalyzes the reaction (300)(303). Dephosphorylation leads to 7,8-dihydro-D-neopterin (304), which is then cleaved in the side-chain to 6-hydroxymethyl-7,8-dihydropterin (305), the direct precursor of 7,8-dihy-dropteroic acid and 7,8-dihydrofolic acid (224). The alcohol (305) requires ATP and Mg " for the condensation with p-aminobenzoic and p-aminobenzoylglutamic acid, indicating pyrophosphate formation to (306) prior to the substitution step. 

Stabler, A.F., The Slip Factor of a Radial Bladed Centrifugal Compressor, ASME Paper No. 64-GTP-l. 

Figure 13.2 Activated G protein receptors, here represented as seven red transmembrane helices, catalyze the exchange of GTP for GDP on the Gapy trimer. The then separated Ga-GTP and Gpy molecules activate various effector molecules. The receptor is embedded in the membrane, and Ga, Gpy and G py are attached to the membrane by lipid anchors, and they all therefore move in two dimensions. (Adapted from D. Clapham, Nature 379 297-299, 1996.)...

A failure to turn off GTP-activated Ga has dire consequences. For example, in the disease cholera, cholera toxin produced by the bacterium Vibrio cholerae binds to Ga and prevents GTP hydrolysis, resulting in the continued excretion of sodium and water into the gut. 

Figure 13.4 Schematic diagram (a) and topology diagram (b) of the polypeptide chain of cH-ras p21. The central p sheet of this a/p structure comprises six p strands, five of which are parallel a helices are green, p strands are blue, and the adenine, ribose, and phosphate parts of the GTP analog are blue, green, and ted, respectively. The loop regions that are involved in the activity of this protein are red and labeled Gl-GS. The Gl, G3, and G4 loops have the consensus sequences G-X-X-X-X-G-K-S/T, D-X-X-E, and N-K-X-D, respectively. (Adapted from E.R Pai et al., Nature 341 209-214, 1989.)...

Figure 13.5 A Mg + atom links GTP to the Ras protein. Mg Is coordinated to one oxygen atom each from the p and y phosphates of GTP as well as to the side chains of Set 17 and Thr 35 of Ras. Two water molecules complete the octahedral coordination of Mg.

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