Multiple Intermolecular Interaction Modes of Positively Charged Residues with Adenine in ATP-Binding Proteins

• Published in: Journal of the American Chemical Society Vol. 125; no. 47; pp. 14216 - 14217
• Main Authors: Mao, Lisong, Wang, Yanli, Liu, Yuemin, Hu, Xiche
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26.11.2003
• Subjects: Adenine - chemistry; Adenine - metabolism; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Interactions. Associations; Intermolecular phenomena; Lysine - chemistry; Lysine - metabolism; Models, Molecular; Molecular biophysics; Protein Binding; Proteins - chemistry; Proteins - metabolism; Quantum Theory; Thermodynamics; Binding protein; Molecular association; Theoretical study; Molecular recognition; Molecular interaction; Hartree Fock method; B-Vitamins; Adenine nucleotide; Interaction energy
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja036096p

Adenosine 5‘-triphosphate (ATP) plays an essential role in all forms of life. Molecular recognition of ATP in ATP-binding proteins is a subject of great importance for understanding enzymatic mechanisms and for drug design. We have carried out a large-scale data mining of the Protein Data Bank (PDB) to analyze molecular determinants for recognition of ATP, in particular, the adenine base, by ATP-binding proteins. A novel distribution pattern of charged residues around the adenine base was discovered:  lysine residues tend to occupy the major groove N7 side of the adenine base, and the arginine residues situate preferentially above or below the adenine bases. Such an arrangement is advantageous because it facilitates multiple modes of intermolecular interactions, that is, cation−π interactions and a hydrogen bond between lysine and adenine, and cation−π and π−π stacking interactions between arginine and adenine. For the two representative Lys···Adenine and Arg···Adenine interactions, intermolecular interaction energies were subsequently analyzed by means of the supermolecular approach at the MP2 level with solvation free energy correction using the SM5.42R model of Cramer and Truhlar, which gave rise to significant interaction strengths.