Probing the energetic and structural role of amino acid/nucleobase cation-π interactions in protein-ligand complexes
Probing the energetic and structural role of amino acid/nucleobase cation-π interactions in protein-ligand complexes
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DOI：
10.1074/jbc.m205719200
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发表时间：
2002-10-25
影响因子：
4.8
通讯作者：
Rooman, M
中科院分区：
文献类型：
--
作者：
Biot, C;Buisine, E;Rooman, M
使用几何标准，系统地搜索与含有核酸碱基的配体分子结合的蛋白质结构，以寻找碱基与其上方带正电或部分带电的侧链基团之间的阳离子- π相互作用。这种相互作用在38%的复合物中被发现，因此比pi-pi堆叠相互作用更频繁。此外，它们在相关蛋白的家族中保守性很好。绝大多数阳离子- π接触涉及Ade碱基，因为它们构成了迄今为止最常见的配体构建块；Arg-Ade;最常见的阳离子对。所有记录对在MP2水平上进行从头算能量计算。虽然涉及Arg或Lys侧链携带的净正电荷的阳离子- π相互作用在能量上是最有利的，但由于电子相关能的贡献，涉及Asn和Gln侧链氨基的部分正电荷的阳离子- π相互作用（有时称为氨基- π相互作用）也有利。在一些配合物中发现了与核碱基同时结合到两个带电基团或夹在两个芳香基团之间的带电基团的阳离子- π相互作用链。这些基序与不相关蛋白质序列中的特定配体分子的系统关联提出了它们在蛋白质配体结构、稳定性和识别中的作用的问题。
structures of proteins bound to ligand molecules containing a nucleic acid base were systematically searched for cation-pi interactions between the base and a positively charged or partially charged side chain group located above it, using geometric criteria. Such interactions were found in 38% of the complexes and are thus even more frequent than pi-pi stacking interactions. They are moreover well conserved in families of related proteins. The overwhelming majority of cation-pi contacts involve Ade bases, as these constitute by far the most frequent ligand building block; Arg-Ade is; the most frequent cation-pi pair. Ab initio energy calculations at MP2 level were performed on all recorded pairs. Though cation-pi interactions involving the net positive charge carried by Arg or Lys side chains are the most favorable energetically, those involving the partial positive charge of Asn and Gln side chain amino groups (sometimes referred to as amino-pi interactions) are favorable too, owing to the electron correlation energy contribution. Chains of cation-pi interactions with a nucleobase bound simultaneously to two charged groups or a charged group sandwiched between two aromatic moieties are found in several complexes. The systematic association of these motifs with specific ligand molecules in unrelated protein sequences raises the question of their role in protein-ligand structure, stability, and recognition.