Interactions of Ribosome and Macrolide Antibiotics by NMR and Modeling (CROSBI ID 524897)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa
Podaci o odgovornosti
Novak, Predrag
engleski
Interactions of Ribosome and Macrolide Antibiotics by NMR and Modeling
NMR techniques have become an invaluable tool for studying receptor-ligand interactions in general and play a major role in conformational analysis and structure-based inhibotor design. NMR spectroscopy allows one to observe the structure and flexibility of receptors (usually proteins) and the dynamics of their interactions with other molecules. Macrolide antibiotics exert their activity by binding to 50S ribosomal subunit and thus inhibit bacterial protein biosynthesis. Understanding the mechanism by which macrolides and ribosomes interact is crucial for the design of novel molecules with bioactivity. Recently available crystal structures of some ribosome- macrolide complexes have thrown new light on the binding mechanisms and hence provide a good basis for the design of new ligands and inhibitors. However, discrepancies between the structures obtained for halophilic archeon H. marismortui and D. radiodurans have been noticed and therefore additional efforts are needed to resolve this issue. NMR can provide further information regarding ribosome-macrolide interactions. Hence, a strategy which combine NMR parameterts such as spin-spin coupling constants, nOe and relaxation times coupled with molecular modelling is employed here to study free conformations of macrolides. Furthermore, the application of transferred nOe and STD (saturation transfer difference) experiments allows for the determination of the bound state conformation and binding epitopes. The knowledge gained from NMR studies in conjunction with chrystalographic data can serve as a platform for design of novel compounds with an improved biological profile.
ribosome-macrolide interactions ; NMR ; Modeling
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Podaci o prilogu
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2006.
objavljeno
Podaci o matičnoj publikaciji
DU NMR 2006 The fifth International DU NMR course and conference
Podaci o skupu
DU NMR 2006 The Fifth International DU NMR Course and Conference
pozvano predavanje
02.11.2006-05.11.2006
Mali Ston, Hrvatska