Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 8, Issue 6, Pages 1225-1243Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0968-0896(00)00081-X
Keywords
-
Ask authors/readers for more resources
Two important lincosamide antibiotics, lincomycin and clindamycin were studied in the complex state with the bacterial ribosome after a conformational analysis by H-1 and C-13 NMR spectroscopy and molecular modelling of the unbound molecules. Lincosamide-ribosome interactions were investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY), resulting in a bound structure compatible with the experimental NMR data. The results compared with the conformational analysis of the substrates in solution indicate that specific conformations are preferred in the bound state. Clindamycin, the more bioactive antibiotic studied, displayed a stronger NMR response than lincomycin showing that in lincosamide-ribosome interactions, a low affinity binding level is associated to the tight binding one and is related to biological activity. This study shows that conformation plays an essential role for the low affinity binding site. Superimposition of lincosamide, macrolide and ketolide bound structures exhibited conformational similarities in a particular fragment which is in agreement with a hypothesis of partial overlapping lincosamide and macrolide binding sites. (C) 2000 Elsevier Science Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available