INTERLOCKING STRUCTURAL MOTIFS MEDIATE MOLECULAR DISCRIMINATION BY A THEOPHYLLINE-BINDING RNA

Citation
Gr. Zimmermann et al., INTERLOCKING STRUCTURAL MOTIFS MEDIATE MOLECULAR DISCRIMINATION BY A THEOPHYLLINE-BINDING RNA, Nature structural biology, 4(8), 1997, pp. 644-649
Citations number
46
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
10728368
Volume
4
Issue
8
Year of publication
1997
Pages
644 - 649
Database
ISI
SICI code
1072-8368(1997)4:8<644:ISMMMD>2.0.ZU;2-X
Abstract
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.