Inhibition of protein synthesi

Mechanism of Action. THie earliest studies on the mechanism of action of lincomycin showed that lincomycin had the immediate effect on Staphjlococcus aureus of complete inhibition of protein synthesis (23). TThis inhibition results from the blocking of the peptidyltransferase site of the SOS subunit of the bacterial ribosome (24). Litde effect on DNA and RNA synthesis was observed. 

It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

One example of a naturally occurring diazirine, duazomycin A (137 Scheme 11.20), has been reported, isolated in 1985 from a Streptomyces species during a screen for herbicidal compounds [196], It was fotind to inhibit de novo starch synthesis and it was suggested that this is due to direct inhibition of protein synthesis. Duazomycin A is structurally related to 6-diazo-5-oxo-L-norleucine (138), also reported as a natural product from Streptomyces [197], which acts as a glutamine antagonist and inhibits purine biosynthesis [198],... 

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

Shiga toxins and related toxins from E. coli No proteins ( ) 28S rRNA A/-glycosidase Cleavage of 28S rRNA Inhibition of protein synthesis... 

Dhindsa, R.S. Cleland, R.E. (1975). Water stress and protein synthesis. I. Differential inhibition of protein synthesis. Plant Physiology, 55, 778-81. 

Inhibition of protein synthesis is the antibacterial mechanism shared by most groups of antibiotics, though the exact action differs. 

Mupirocin is a topical antibiotic that inhibits isoleucyl tRNA synthetase with the subsequent inhibition of protein synthesis. Mupirocin has become a mainstay in the treatment of Staph, aureus infection and colonization during hospital outbreaks, and it is in this organism that acquired resistance has arisen (Gilbart etal. 1993). 

The reported (14) mechanisms of action of allelochemlcals Include effects on root ultrastructure and subsequent Inhibition of Ion absorption and water uptake, effects on hormone-induced growth, alteration of membrane permeability, changes In lipid and organic acid metabolism, inhibition of protein synthesis and alteration of enzyme activity, and effects on stomatal opening and on photosynthesis. Reduced leaf water potential Is one result of treatment with ferulic and p-coumaric acids (15). Colton and Einhellig (16) found that aqueous extracts of velvetleaf (Abutllon theophrastl Medic.) Increased diffusive resistance In soybean fGlycine max. (L.) Merr.] leaves, probably as a result of stomatal closure. In addition, there was evidence of water stress and reduced quantities of chlorophyll In Inhibited plants. 

Honjo, J., Nishizuka, Y., Hayaishi, O., and Kato, I. (1968) Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J. Biol. Cbem. 243, 3553-3555. 

EHEC all ages/primarily in US, Canada, Europe, South America and Japan 12-60h acute bloody (hemorrhagic colitis in 31— 61%) occasionally nonbloody diarrhea SLT-I and -II - bloodstream - inhibition of protein synthesis - endothelial cell damage - microvascular thrombosis - hemolytic-uremic syndrome... 

Gasperi-Campani, Anna, Luigi Barbieri, Enzo Lorenzoni, Lucio Montanaro, Simonetta Sperti, Eugenio Bonetti, and Fiorenzo Stirpe. "Modeccin, the Toxin of Adenia digitata Purification, Toxicity and Inhibition of Protein Synthesis In Vitro." Biochemical Journal 174 (1978) 491-96. 

Costa, L.G. and R. Sulaiman. 1986. Inhibition of protein synthesis by trimethyltin. Toxicol. Appl. Pharmacol. 86 189-196. 

DT Corynebacterium AB GTPases Elongation Factor-2 Inhibition of protein synthesis Diphtheria... 

Incorporation into nucleic acids Inhibition of protein synthesis Interference with co-factors Summary... 

Kinase inhibitors such as H7, which inhibits serine threonine kinases, resulted in sustained JAK2/STAT activation, suggesting that besides protein dephosphorylation, protein phosphorylation is also required. Furthermore, both inhibition of protein synthesis with cycloheximide and inhibition of... 

Inhibition of protein synthesis in microorganisms (aminoglycosides, erythromycin, clindamycin, chloramphenicol, and tetracyclines). 

Pharmacology The tetracyclines are bacteriostatic. They exert their antimicrobial effect by inhibition of protein synthesis. Tetracyclines are active against a wide range of gram-positive and gram-negative organisms. 

We conclude that by 3 3/4 hr after the onset of ozonation the inhibition of protein synthesis has become a factor in the overall physiological disturbance in the soybean trifoliate leaf. However, this was not necessarily the case for the earlier (55-100 min) events described in Figure 6. That data showed that protein synthesis was depressed by as little as 15 min of ozone exposure, but not depressed further as ozone exposure was lengthened to 90 min. What we have been unable to show by the overloading experiment is the exclusivity, immediately following ozonation for brief periods, of the inhibition of amino acid... 

The hepatotoxic effects of carbon tetrachloride have been widely studied in animals. Indeed, carbon tetrachloride is used as a model chemical in many laboratory investigations of the basic mechanism of action of hepatotoxic chemicals. Oral exposure to carbon tetrachloride has been observed to result in a wide spectrum of adverse effects on the liver, the most prominent of which are destruction of the smooth and rough endoplasmic reticulum and its associated enzyme activities (Reynolds and Yee 1968), inhibition of protein synthesis (Lutz and Shires 1978), impaired secretion of triglycerides with resultant fat accumulation (Fischer-Nielsen et al. 1991 Recknagel and Ghoshal 1966 Recknagel and Glende 1973 Waterfield et al. 1991), centrilobular necrosis (Blair et al. 1991 Reynolds and Yee 1968 Waterfield et al. 1991 Waterfield et al. 1991 Weber et al. 1992), and eventually fibrosis and cirrhosis (Allis et al. 1990 Bruckner et al. 1986 Fischer-Nielsen et al. 1991 Weber etal. 1992). 

Although all tetracyclines have a similar mechanism of action, they have different chemical structures and are produced by different species of Streptomyces. In addition, structural analogues of these compounds have been synthesized to improve pharmacokinetic properties and antimicrobial activity. While several biological processes in the bacterial cells are modified by the tetracyclines, their primary mode of action is inhibition of protein synthesis. Tetracyclines bind to the SOS ribosome and thereby prevent the binding of aminoacyl transfer RNA (tRNA) to the A site (acceptor site) on the 50S ri-bosomal unit. The tetracyclines affect both eukaryotic and prokaryotic cells but are selectively toxic for bacteria, because they readily penetrate microbial membranes and accumulate in the cytoplasm through an energy-dependent tetracycline transport system that is absent from mammalian cells. 

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