|
Figure 5.
Figure 5. Comparison of the Interactions of Different
Macrolides with the Ribosome(A) Carbomycin (red), tylosin
(orange), spiramycin (yellow), and azithromycin (blue) bind the
ribosome in an almost identical fashion and cover G2099 (A2058)
and A2100 (2059) (green spheres). The lactone ring is extended
further into the tunnel by mycinose on tylosin and forosamine on
spiramycin. The disaccharide moiety extends the 16-membered
macrolides in the opposite direction toward the catalytic
center. Upon 16-membered macrolide binding (but not
azithromycin), the base of A2103 (2062) (dark green) moves
(curved white line) from its location against the wall of the
exit tunnel to an extended conformation (light green sticks) and
forms a covalent bond with the macrolide (orange sticks). The
isobutyrate group of carbomycin A (red) reaches into the tRNA
A-site (dark blue and purple spheres). The mycinose moiety of
tylosin (orange) contacts protein L22. The forosamine moiety of
spiramycin (yellow) contacts L4. The cladinose sugar of
azithromycin binds in a fourth sugar binding pocket. These three
macrolides were aligned by least squares superimposition of the
phosphates of ribosomal RNA.(B) Alignment of erythromycin
(white) bound to the D. radiodurans large subunit
(Schlünzen et al., 2001) with azithromycin (blue) bound to
the H. marismortui large subunit.
|
