title: Specific alterations of the EF-Tu polypeptide chain considered in the light of its three-dimensional structure.
abstract: Specific alterations of the elongation factor Tu (EF-Tu) polypeptide chain have been identified in a number of mutant species of this elongation factor. In two species, Ala-375, located on domain II, was found by amino acid analysis to be replaced by Thr and Val, respectively. These replacements substantially lower the affinity of EF-Tu.GDP for the antibiotic kirromycin. Since kirromycin can be cross-linked to Lys-357, also located on domain II but structurally very far from Ala-375, these data suggest that the replacements alter the relative position of domains I and II. The Ala-375 replacements also lower the dissociation rates of the binary complexes EF-Tu.GTP and the binding constants for EF-Tu.GTP and Phe-tRNA. It is conceivable that these effects are also mediated by movements of domains I and II relative to each other. Replacement of Gly-222 by Asp has been found in another mutant by DNA sequence analysis of the cloned tufB gene, coding for this mutant EF-Tu. Gly-222 is part of a structural domain, characteristic for a variety of nucleotide binding enzymes. Its replacement by Asp does not abolish the ability of EF-Tu to sustain protein synthesis. It increases the dissociation rate of EF-Tu.GTP by approximately 30%. In the presence of kirromycin this mutant species of EF-Tu.GDP does not bind to the ribosome, in contrast to its wild-type counterpart. A possible explanation is now open for experimental verification.
mesh_terms: D000596:Amino Acids / Q000032:analysis; D004262:DNA Restriction Enzymes; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D007700:Kinetics; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008958:Models, Molecular; D009154:Mutation; D010444:Peptide Elongation Factor Tu; D010445:Peptide Elongation Factors / Q000235:genetics*; D010446:Peptide Fragments / Q000032:analysis; D014176:Protein Biosynthesis / Q000187:drug effects; D011487:Protein Conformation; D011728:Pyridones / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D000596:Amino Acids; D010445:Peptide Elongation Factors; D010446:Peptide Fragments; D011728:Pyridones; D008769:Methylnitronitrosoguanidine; D004262:DNA Restriction Enzymes; D010444:Peptide Elongation Factor Tu; C008536:mocimycin