Abstract
Four hundred twenty-eight high-resolution DNA–protein complexes were chosen for a bioinformatics study. Although 164 crystal structures (38% of those searched) contained no interactions, 574 discrete π–contacts between the aromatic amino acids and the DNA nucleobases or deoxyribose were identified using strict criteria, including visual inspection. The abundance and structure of the interactions were determined by unequivocally classifying the contacts as either π–π stacking, π–π T-shaped or sugar–π contacts. Three hundred forty-four nucleobase–amino acid π–π contacts (60% of all interactions identified) were identified in 175 of the crystal structures searched. Unprecedented in the literature, 230 DNA–protein sugar–π contacts (40% of all interactions identified) were identified in 137 crystal structures, which involve C–H···π and/or lone–pair···π interactions, contain any amino acid and can be classified according to sugar atoms involved. Both π–π and sugar–π interactions display a range of relative monomer orientations and therefore interaction energies (up to –50 (–70) kJ mol−1 for neutral (charged) interactions as determined using quantum chemical calculations). In general, DNA–protein π-interactions are more prevalent than perhaps currently accepted and the role of such interactions in many biological processes may yet to be uncovered.
Highlights
DNA–protein complexes were identified in the protein data bank (PDB) using similar criteria to those previously used in the literature to detect nucleobase–amino acid – contacts (Supplementary Figure S3) [8,30]
Despite the fact that DNA sugar– contacts with aromatic amino acid residues are rarely discussed in the literature, the importance of analogous carbohydrate– interactions in many fields [62,63,64,65,66,67,68,69,70,71,72,73,74] coupled with the number of contacts found in nature in the present study suggests that these interactions may be important for biological processes, either by providing stability to DNA–protein complexes, facilitating DNA binding/recognition, or possibly even having a greater role
The present contribution suggests that nucleobase–amino acid contacts are wider spread than perhaps originally believed and highlights the role of novel interactions between the deoxyribose moiety and the aromatic amino acids, which parallel the carbohydrate– contacts identified in glycobiology [62,63,64,65,66,67,68]
Summary
DNA–protein interactions are evident in other critical cellular processes, such as the repair of DNA damage caused by carcinogenic compounds or UV light [1,2,3,4]. Contacts between DNA and proteins are typically noncovalent, which allows the resulting complex to perform necessary biological functions, yet readily degrade such that both biomolecules can provide additional function to the cell [5,6]. Understanding each class of DNA–protein contacts will provide a greater appreciation of critical cell functions and open the door for the development of new medicinal and biological applications, including rational drug design [10,11,12] and the control of gene expression [13,14,15,16]
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