title: On the mode of inhibition of eukaryotic protein synthesis by ADP-ribosylation of elongation factor 2.
abstract: The exchange of free guanine nucleotides with guanine nucleotides bound to elongation factor 2 (EF-2) and to the EF-2-ribosome complex, and the effect of ADP-ribosylation of the EF-2 thereon, were investigated by nitrocellulose filter assay. Under the experimental conditions, stoichiometric amounts of guanine nucleotides were bound, in particular, to ternary complexes of EF-2 with biphasic kinetics. The exchange kinetics were similarly biphasic in all cases. Ribosomes appeared to have variable effects on the exchange kinetics, depending on the type of nucleotide bound. Thus, in their presence, the rate and magnitude of the fast exchange of nucleotides revealed increasing values in the order GTP (GXP) > GTP gamma S > GDP. ADP-ribosylation had no inhibitory effect on the binding of guanine nucleotides to EF-2 or to the EF-2-ribosome complex but reduced significantly the fast exchange of GTP (GXP) and GTP gamma S bound to the EF-2-ribosome complex. The effect of ADP-ribosylation on the fast exchange of GDP in binary and ternary complexes was less pronounced. The mechanism of inhibition of protein synthesis by ADP-ribosylation of EF-2 is discussed in view of these data.
authors.affiliation: Department of Biophysics, I. U. Istanbul Faculty of Medicine, Capa-Istanbul, Turkey. nurtenr@istanbul.edu.tr
authors.forename: R
authors.initials: R
authors.lastname: Nurten
authors.forename: I
authors.initials: I
authors.lastname: Albeniz
authors.forename: E
authors.initials: E
authors.lastname: Bermek
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D003101:Collodion; D005374:Filtration / Q000295:instrumentation; D006150:Guanine Nucleotides / Q000378:metabolism; D007700:Kinetics; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D012270:Ribosomes / Q000378:metabolism
chemical_list: D006150:Guanine Nucleotides; D020652:Peptide Elongation Factor 2; D011506:Proteins; D000246:Adenosine Diphosphate Ribose; D003101:Collodion