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C. Cocito, G. Chinali, Molecular mechanism of action of virginiamycin-like antibiotics (synergimycins) on protein synthesis in bacterial cell-free systems, Journal of Antimicrobial Chemotherapy, Volume 16, Issue suppl_A, 1985, Pages 35–52, https://doi.org/10.1093/jac/16.suppl_A.35
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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 .