The binding of kirromycin to elongation factor Tu. Structural alterations are responsible for the inhibitory action.
The influence of kirromycin on the elongation factor Tu (EF-Tu) in its binary and ternary complexes was investigated. The equilibrium constant for the binding of the antibiotic to EF-Tu . GDP and EF-Tu . GTP was determined by circular dichroism titrations to be 4 x 10(6) M-1, and to EF-Tu . GTP . aa-tRNA by a combination of circular dichroism titrations and hydrolysis protection experiments to be 2 x 10(6) M-1. In the presence of kirromycin the binding of aminoacyl-tRNAs to EF-Tu . GTP is weakened by a factor of two. The antibiotic changes the conformation of the ternary complex in such a way that the aminoacyl moiety of the aminoacyl-tRNA is more accessible to the non-enzymatic hydrolysis. It is concluded that this structural alteration is responsible for the inhibitory action of the antibiotic.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002942:Circular Dichroism; D004926:Escherichia coli / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D010445:Peptide Elongation Factors; D011728:Pyridones
D000900:Anti-Bacterial Agents; D010445:Peptide Elongation Factors; D011728:Pyridones; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C008536:mocimycin