Protein synthesis elongation

This reaction is reversible when conducted in vitro, but under the conditions of pH and nicotinamide concentration that exist in the cell, it is irreversible. Thus, diphtheria toxin kills cells by irreversibly destroying the ability of EF-2 to participate in the translocation step of protein synthesis elongation. A number of other protein toxins have subsequently been found to ADP-ribosylate and inactivate cellular proteins involved in other essential cellular pathways. For example, cholera and pertussis toxins ADP-ribosylate and inactivate proteins important to cAMP metabolism. 

Elongation factors. Protein factors uniquely required during the elongation phase of protein synthesis. Elongation factor G (EF-G) brings about the movement of the peptidyl-tRNA from the A site to the P site of the ribosome. 

GE2270A 394 is an antibiotic produced by Planobispora rosea ATCC 537731. It inhibits Gram-positive bacteria and anaerobes by acting on the protein synthesis elongation factor (EF) <1991JAN693, 1995T4867>. It contains proline, serine, glycine, two thiazolyl amino acids, and a heterocyclic centerpiece of a trisubstituted pyridine, all in a macrocyclic array. 

E. coli membranes contains zinc, which is required for full activity. A functional role for zinc in protein synthesis elongation factor 1 from rat liver has been inferred from the observation that 0.3 mM 1,10-phenanthroline completely abolishes guano-sine 5 -triphosphate binding to EFl there is one zinc per molecule (54 000 Daltons). ... 

Nilsson L and Nygard O (1986). The mechanism of the protein-synthesis elongation cycle in eukaryotes. Effect of ricin on the ribosomal interaction with elongation factors. Eur J Biochem, 161, 111-117. 

Guanosine diphosphate EF-Tu (protein synthesis elongation factor) complex Haemoglobin... 

Protein synthesis initiation by IF-2 Protein synthesis elongation hy EF-Tu and EF-G Polyamine synthesis by ornithine decarboxylase rRNA synthesis by RNA polymerase Acetyl-CoA carboxylase"... 

A different kind of enzyme, translocase [80700-39-6], which transfers a fragment of NAD to the protein—synthesis factor (elongation factor 2), is catalyzed by diphtheria toxin, thereby inhibiting protein synthesis (43). In tumor cells, the rate of protein synthesis is 100 to 1000 times more sensitive to diphtheria toxin than the analogous process in normal cells (41) therefore, diphtheria toxin is selectively toxic to tumor cells. 

Protein synthesis 1 Elongation factor-2 kinase l Translation elongation All cells ... 

Diphtheria toxin, Pseudomonas exotoxin A Elongation factor 2 ADP-ribosylation Inhibition of protein synthesis (diphtheria, Pseudomonas infection)... 

Increased protein synthesis Increased amino acid uptake/increased translation of mRNA Akt-mediated stimulation of system A amino acid transporter and stimulation of mRNA-translation through activation of p70S6kinase and elongation initiation factor 4 (elF4). Possible involvement of atypical PKCs... 

LIKE TRANSCRIPTION, PROTEIN SYNTHESIS CAN BE DESCRIBED IN THREE PHASES INITIATION, ELONGATION, TERMINATION... 

Figure 38-8. Diagrammatic representation of the peptide elongation process of protein synthesis. The small circles labeled n - 1, n, n -I-1, etc, represent the amino acid residues of the newly formed protein molecule. EFIA and EF2 represent elongation factors 1 and 2, respectively. The peptidyl-tRNA and aminoacyl-tRNA sites on the ribosome are represented by P site and A site, respectively.

Fig. 8.4 Outline of the main events in protein synthesis initiation, elongation, translocation and termination. AUG is an initiation codon on the mRNA it codes for Af-fomiylmelhionine and initiates the formation of the 70S rihosome. UAG is a termination codon it does not code for any amino acid and brings about termination of protein synthesis.

Shastry, M., Nielsen, J., Ku, T., Hsu, M. J., Liberator, P., Anderson, J., Schmatz, D., and Justice, M. C. (2001). Species-specific inhibition of fungal protein synthesis by sordarin Identification of a sordarin-specificity region in eukaryotic elongation factor 2. Microbiology 147, 383-390. 

A third type of bacterial toxin, diphtheria toxin, catalyzes the ADP-ribosylation of eukaryotic elongation factor (EFTU), a type of small G protein involved in protein synthesis (Table 19-2). The functional activity of the elongation factor is inhibitedby this reaction. Finally, a botulinum toxin ADP-ribosylates and disrupts the function of the small G protein Rho, which appears to be involved in assembly and rearrangement of the actin cytoskeleton (Table 19-2). These toxins maybe involved in neuropathy (see Ch. 36) and membrane trafficking (see Ch. 9). 

Diphtheria causes a demyelinative neuropathy. Coryne-bacterium diphtheriae colonizes the pharynx or open wounds, and secretes a protein exotoxin. The B subunit of this exotoxin binds to plasma membranes and facilitates entry into cytosol of the A subunit, which catalyzes ADP-ribosylation, and inactivation of an elongation factor required for protein synthesis. Cardiac muscle and Schwann cells are particularly susceptible to this toxin, and hence patients with diphtheria develop cardiomyopathy and demyelinative polyneuropathy [20]. While diphtheria is now uncommon because of childhood immunization against C. diphtheriae, the disruption in preventative medicine programs caused by disintegration of the Soviet Union was followed by a substantial incidence of diphtheritic polyneuropathy in Russia. 

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