Published online 7 October 2005
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Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: role of the number of rings and positive charges in the specific binding leading to miscoding
Institut de biologie moléculaire et cellulaire du CNRS, UPR9002 ‘Architecture et Réactivité de l'ARN’, Université Louis Pasteur F-67084 Strasbourg, France 1Vernalis (R&D) Granta Park, Cambridge, CB1 6GB, UK
*To whom correspondence should be addressed. Tel: +33388417046; Fax: +33388601822; Email: e.westhof{at}ibmc.u-strasbg.fr
Received July 24, 2005. Revised September 7, 2005. Accepted September 7, 2005.
The crystal structures of six complexes between aminoglycoside antibiotics (neamine, gentamicin C1A, kanamycin A, ribostamycin, lividomycin A and neomycin B) and oligonucleotides containing the decoding A site of bacterial ribosomes are reported at resolutions between 2.2 and 3.0 Å. Although the number of contacts between the RNA and the aminoglycosides varies between 20 and 31, up to eight direct hydrogen bonds between rings I and II of the neamine moiety are conserved in the observed complexes. The puckered sugar ring I is inserted into the A site helix by stacking against G1491 and forms a pseudo base pair with two H-bonds to the Watson–Crick sites of the universally conserved A1408. This central interaction helps to maintain A1492 and A1493 in a bulged-out conformation. All these structures of the minimal A site RNA complexed to various aminoglycosides display crystal packings with intermolecular contacts between the bulging A1492 and A1493 and the shallow/minor groove of Watson–Crick pairs in a neighbouring helix. In one crystal, one empty A site is observed. In two crystals, two aminoglycosides are bound to the same A site with one bound specifically and the other bound in various ways in the deep/major groove at the edge of the A sites.
Present addresses: Fareed Aboul-ela, Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA
Quentin Vicens, Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309-0215, USA
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