Elongation factors

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)... 

Ping YH, Chu CY, Gao H, Jacque JM, Stevenson M, Rana TM (2004) Modulating HlV-1 replication by RNA interference directed against human transcription elongation factor SPT5, Retro-virology 1 46... 

The general topology of rubredoxins is also observed in the general zinc-ribbon motif in RNA polymerases or in transcription factors (59). The first published zinc-ribbon structure was that of the nucleic-acid binding domain of human transcriptional elongation factor TFIIS (PDB file ITFI) 40). These zinc binding domains and rubredoxins... 

Elongation is a cycUc process on the ribosome in which one amino acid at a time is added to the nascent peptide chain. The peptide sequence is determined by the order of the codons in the mRNA. Elongation involves several steps catalyzed by proteins called elongation factors (EFs). These steps are (1) binding of aminoacyl-tRNA to the A site, (2) peptide bond formation, and (3) translocation. 

The now deacylated tRNA is attached by its anticodon to the P site at one end and by the open GGA tail to an exit (E) site on the large ribosomal subunit (Figure 38-8). At this point, elongation factor 2 (EE2) binds to and displaces the peptidyl tRNA from the A site to the P site. In turn, the deacylated tRNA is on the E site, from which it leaves the ribosome. The EF2-GTP complex is hydrolyzed to EF2-GDP, effectively moving the mRNA forward by one codon and leaving the A site open for occupancy by another ternary complex of amino acid tRNA-EFlA-GTP and another cycle of elongation. 

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.

In diphtheria, the organism C. diphtheriae eonfmes itself to epithelial surfaces of the nose and throat and produces a powerfiil toxin which affects the elongation factor involved in protein biosynthesis. The heart and peripheral nerves are particularly affected resulhng in myocarditis (inflammation of the myocardium) and neuritis (inflammation of a nerve). Little damage is produeed at the infective site. 

Bacterial ribosome function Aminoglycosides Tetracyclines Chloramphenicol Macrolides, azalides Fusidic acid Mupirocin Distort SOS ribosomal subunit Block SOS ribosomal subunit Inhibits peptidyl transferase Block translocation Inhibits elongation factor Inhibits isoleucyl-tRNA synthesis No action on 40S subunit Excluded by mammalian cells No action on mammalian equivalent No action on mammalian equivalent Excluded by mammalian cells No action on mammalian equivalent... 

This prevents further ineorporation of aminoaeyl-tRNA by bloeking the binding of EF-Tu GTP. Like the tetraeyelines, fusidie aeid owes its seleetive antimierobial aetion to active uptake by bacteria and exclusion fiom manunalian cells. The equivalent elongation factor in mammalian cells, EF-2 is susceptible to fusidie acid in cell-free systems. 

Protein phosphorylation Calmodulin kinase I ATI Elongation factor-2 kinase Phosphorylase kinase Myosin Light Chain kinase... 

Wang, L., and Proud, C. G. (2002b). Regulation of the phosphorylation of elongation factor 2 by MEK-dependent signaling in adult rat cardiomyocytes. FEBS Lett. 531, 285—289. 

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. 

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