Gr. Zimmermann et al., INTERLOCKING STRUCTURAL MOTIFS MEDIATE MOLECULAR DISCRIMINATION BY A THEOPHYLLINE-BINDING RNA, Nature structural biology, 4(8), 1997, pp. 644-649
To visualize the interplay of RNA structural interactions in a ligand
binding site, we have determined the solution structure of a high affi
nity RNA-theophylline complex using NMR spectroscopy The structure pro
vides insight into the ability of this in vitro selected RNA to discri
minate theophylline from the structurally similar molecule caffeine. N
umerous RNA structural motifs combine to form a well-ordered binding p
ocket where an intricate network of hydrogen bonds and stacking intera
ctions lock the theophylline into the complex, Two internal loops inte
ract to form the binding site which consists of a sandwich of three ba
se triples, The complex also contains novel base-zipper and 1-3-2 stac
king motifs, in addition to an adenosine platform and a reversed sugar
, An important feature of the RNA is that many of the conserved core r
esidues participate in multiple overlapping tertiary interactions. Thi
s complex illustrates how interlocking structural motifs can be assemb
led into a highly specific ligand-binding site that possesses high lev
els of affinity and molecular discrimination.