title: Nucleotide regulation of a eukaryotic protein synthesis initiation complex;.
abstract: Formation of a ternary initiation complex containing Met-tRNAf, GTP and eukaryotic initiation factor 2, is the first step in sequential assembly of the initiation complex. The concentration of GTP required for half maximal formation of the ternary complex is 2.5 with 10(-6) M. GDP is a potent competitive inhibitor of ternary complex formation with Ki = 3.4 with 10(-7) M. The nucleotide binding site on eukaryotic initiation factor 2 demonstrates relative specificity for GDP with KD(GDP) = 3.0 with 10(-8) M; 100-fold higher concentrations of GTP than GDP are required for displacement of either [(3)H]GDP or [(3)h]gtp from the necleotide binding site. An ATP-dependent stimulation of ternary complex formation observed in partially purified initiation factor preparations is due to nucleoside diphosphate kinase (EC 2.7.4.6) which serves to remove inhibitory levels of GDP by phosphorylation with ATP. Since GTP is hydrolyzed to GDP during protein synthesis, this provides a mechanism by which the ATP:ADP ratio may regulate the rate of initiation of protein synthesis.
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D008099:Liver; D008715:Methionine; D008968:Molecular Conformation; D008970:Molecular Weight; D009711:Nucleotides; D010448:Peptide Initiation Factors / Q000302:isolation & purification; D010770:Phosphotransferases / Q000494:pharmacology; D012343:RNA, Transfer; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes; D012441:Saccharomyces cerevisiae
chemical_list: D006150:Guanine Nucleotides; D009711:Nucleotides; D010448:Peptide Initiation Factors; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D012343:RNA, Transfer; D008715:Methionine; D010770:Phosphotransferases