antibiotic inhibits intrinsic GTPase and that stimulated by ribosomes; thiazolyl-peptide antibiotic, inhibits both the intrinsic GTPase of elongation factor 1alpha and that stimulated by ribosomes. The M domain is the region of the enzyme most responsible for the interaction with GE2270A
competitive inhibition of intrinsic GTPase, inhibition of archaeal protein synthesis in vitro, even though the concentration required to get inhibition is higher than that required for the eubacterial and eukaryal systems
oxidation of EF-G inhibits the function of EF-G on the ribosome. With hydrogen peroxide, neither the insertion of EF-G into the ribosome nor single-cycle translocation activity in vitro is affected, while the GTPase activity and the dissociation of EF-G from the ribosome are suppressed when EF-G is oxidized. The synthesis of longer peptides is suppressed to a greater extent than that of a shorter peptide when EF-G is oxidized
the antibiotic effectively inhibits translocation of mRNA and tRNAs on the ribosome in both bacteria and eukaryotes. Hygromycin B blocks the toeprint shift induced by eEF2 and deacylated tRNA
IF2alpha is phosphorylated at Ser51 by four kinases in what is collectively known as the integrated stress response (ISR). Phosphorylation of the eIF2alpha subunit in response to various cellular stresses converts eIF2-GDP into a competitive inhibitor of eIF2B, which triggers the integrated stress response (ISR)
mixed inhibition. The inhibition level depends on the antibiotic concentration, even though a complete inhibition is not reached even in the presence of 0.120 mM antibiotic, a concentration corresponding to about 200fold molar excess over the elongation factor
KIR, an antibiotic that directly binds to the interface of EF-Tu domains D1 and D3 and prevents dissociation of EF-Tu from the ribosome and from the amino acid-tRNA after GTP hydrolysis. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. With KIR bound, the overall conformation of EF-Tu remains close to the GTP-bound conformation after hydrolysis, both on and off the ribosome
KIR, an antibiotic that directly binds to the interface of EF-Tu domains D1 and D3 and prevents dissociation of EF-Tu from the ribosome and from the amino acid-tRNA after GTP hydrolysis. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. With KIR bound, the overall conformation of EF-Tu remains close to the GTP-bound conformation after hydrolysis, both on and off the ribosome
the antibiotic is able to reduce in vitro the rate of protein synthesis however, the concentration of pulvomycin leading to 50% inhibition (173 mM) is two order of magnitude higher but one order lower than that required in eubacteria and eukarya, respectively. Pulvomycin is able to decrease the affinity of the elongation factor toward aa-tRNA only in the presence of GTP, to an extent similar to that measured in the presence of GDP
inhibits the ribosome-stimulated GTPase activity of EF-G and EF4. An EF-G mutant lacking domains 4 and 5 is insensitive to the effects of thiostrepton on both GTPase activity and ribosome binding
viomycin and fusidic acid do not prevent GTP hydrolysis, but these antibiotics trap EF-G on the ribosome before or after ribosomal translocation, respectively
in free enzyme EF-G, crucial sensors of switch I and II regions are disordered and become ordered in the complex with a nonhydrolyzable GTP analogue, GDPCP, on the ribosome. This causes a reorientation of EF-G such that the tip of domain IV moves and the CHI state ofthe ribosome is stabilized
ADP-ribosylation of eEF2 domain IV blocks reverse translocation activity of eEF2. ADP-ribosylation may directly interrupt the ability of eEF2 to stabilize the intermediate conformation of the tRNA ends during their movement through the SSU in the course of translocation
3.6.5.3 protein-synthesizing GTPase
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