Dieckmann T, Butcher S E, Sassanfar M, Szostak J W, Feigon J
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California at Los Angeles, 405 Hilgard Ave, Los Angeles, CA 90095, USA.
J Mol Biol. 1997 Oct 24;273(2):467-78. doi: 10.1006/jmbi.1997.1329.
The solution structure of the ATP-binding RNA aptamer has recently been determined by NMR spectroscopy. The three-dimensional fold of the molecule is determined to a large extent by stacking and hydrogen bond interactions. In the course of the structure determination it was discovered that several highly conserved nucleotides in the binding pocket can be substituted while retaining binding under NMR conditions. These surprising findings allow a closer look at the interactions that determine stability and specificity of the aptamer as well as local structural features of the molecule. The binding properties of ATP binder mutants and modified ligand molecules are explored using NMR spectroscopy, column binding studies and molecular modeling. We present additional evidence and new insights regarding the network of hydrogen bonds that defines the structure and determines stability and specificity of the aptamer.
ATP结合RNA适体的溶液结构最近已通过核磁共振光谱法确定。该分子的三维折叠在很大程度上由堆积和氢键相互作用决定。在结构测定过程中发现，结合口袋中的几个高度保守的核苷酸可以被取代，同时在核磁共振条件下仍保留结合能力。这些惊人的发现使我们能够更深入地研究决定适体稳定性和特异性的相互作用以及分子的局部结构特征。使用核磁共振光谱法、柱结合研究和分子建模来探索ATP结合突变体和修饰配体分子的结合特性。我们提供了关于定义适体结构并决定其稳定性和特异性的氢键网络的更多证据和新见解。
