Naslov
Interactions of Ribosome and Macrolide Antibiotics by NMR and Modeling

Autori
Novak, Predrag

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
DU NMR 2006 The fifth International DU NMR course and conference / - , 2006

Skup
DU NMR 2006 The fifth International DU NMR course and conference

Mjesto i datum
Mali Ston, Hrvatska, 02.11.2006. - 05.11.2006

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
ribosome-macrolide interactions ; NMR ; Modeling

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA