Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP.
The antibiotic kirromycin inhibits protein synthesis by binding to EF-Tu and preventing its release from the ribosome after GTP hydrolysis. We have isolated and sequenced a collection of kirromycin resistant tuf mutations and identified thirteen single amino acid substitutions at seven different sites in EF-Tu. These have been mapped onto the 3D structures of EF-Tu.GTP and EF-Tu.GDP. In the active GTP form of EF-Tu the mutations cluster on each side of the interface between domains I and III. We propose that this domain interface is the binding site for kirromycin.
Abdulkarim
F
F
Department of Molecular Biology, Uppsala University, Sweden.
Liljas
L
L
Hughes
D
D
D000596:Amino Acids / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010444:Peptide Elongation Factor Tu / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D011728:Pyridones / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D011728:Pyridones; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D010444:Peptide Elongation Factor Tu; C008536:mocimycin