Molecular mechanism of action of virginiamycin-like antibiotics (synergimycins) on protein synthesis in bacterial cell-free systems
- 1 January 1985
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Antimicrobial Chemotherapy
- Vol. 16 (suppl A) , 35-52
- https://doi.org/10.1093/jac/16.suppl_a.35
Abstract
Synergimycins contain two types of components, A and B, which synergistically inhibit in-vivo protein synthesis. In-vitro , both components interact with 50 S ribosomal subunits. B components bind in stoichiometric amounts ( KA = 2·5 × 10 6 M −1 ): the association constant undergoes a ten-fold increase in the presence of A components. The latter inhibitors act in substoichiometric concentration ( KA = 0·32× 10 6 M −1 and produce lasting ribosome damage due to a conformational alteration requiring proteins L7/L12, L8 and L16. Such alteration entails a permanent block of the peptidyltransferase substrate acceptor site, whereby aminoacyl tRNA enzymically bound to ribosomes is released. Macrolides ( KA = 7·2 × 10 7 M −1 displace ribosome-bound B components, but they are unable to compete in the presence of A components, which reduce both the affinity of ribosomes for macrolides, and the dissociation rate constant of B components. These findings provide a molecular explanation to the synergistic action of A and B components in-vivo .Keywords
This publication has 1 reference indexed in Scilit:
- The in vitro binding of virginiamycin M to bacterial ribosomes and ribosomal subunitsMolecular Genetics and Genomics, 1978