Probing the energetic and structural role of amino acid/nucleobase cation-π interactions in protein-ligand complexes

被引:74
作者
Biot, C
Buisine, E
Kwasigroch, JM
Wintjens, R
Rooman, M
机构
[1] Free Univ Brussels, B-1050 Brussels, Belgium
[2] Univ Sci & Tech Lille Flandres Artois, URRESA 8009, CNRS, Lab Chim Organ & Macromol, F-59655 Villeneuve Dascq, France
[3] Univ Lille 2, CNRS, UMR 8525, Inst Biol Lille,Inst Pasteur Lille, F-59021 Lille, France
关键词
D O I
10.1074/jbc.M205719200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:40816 / 40822
页数:7
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