Antibiotic resistance peptides: interaction of peptides conferring macrolide and ketolide resistance with Staphylococcus aureus ribosomes: conformation of bound peptides as determined by transferred NOE experiments

Biochemistry
L VerdierJean-Pierre Girault

Abstract

Two antibiotic resistance peptides, the E-peptide (MRLFV) and the K-peptide (MRFFV) conferring macrolide and ketolide resistance, respectively, were studied in the complex state with bacterial Staphylococcus aureus ribosomes. Interactions of antibiotic resistance peptides with ribosomes were investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY), suggesting that the peptide-ribosome interaction was associated with the low-affinity binding level. K-Peptide displayed a significantly better response in TRNOEs NMR experiments, in agreement with a better overall antibiotic activity of ketolides. This difference highlights a mimetic effect displayed by the E- and K-peptides. This study shows that conformation plays an essential role for the affinity binding site and, thus, for the resistance mechanism. Specific conformations were preferred in the bound state; their superimposition exhibited a similar cyclic peptidyl chain, while the side chain region varies. The F4 phenyl moiety in E-peptide has moved out of the turn region compared to its folding in the ketolide resistance peptide. In the K-peptide binding surface, the F4 aromatic chain is maintained by stacking with the guanidyl group of the...Continue Reading

References

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Citations

Oct 22, 2003·Current Opinion in Structural Biology·Carol Beth Post
Apr 1, 2003·Nature Structural Biology·Rita BerisioAda Yonath
Dec 10, 2003·Expert Opinion on Emerging Drugs·George G ZhanelDaryl J Hoban

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