Mutations to kirromycin resistance occur in the interface of domains I and III of EF‐Tu·GTP

Abstract
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.