title: Amino acid-base interactions: a three-dimensional analysis of protein-DNA interactions at an atomic level.
abstract: To assess whether there are universal rules that govern amino acid-base recognition, we investigate hydrogen bonds, van der Waals contacts and water-mediated bonds in 129 protein-DNA complex structures. DNA-backbone interactions are the most numerous, providing stability rather than specificity. For base interactions, there are significant base-amino acid type correlations, which can be rationalised by considering the stereochemistry of protein side chains and the base edges exposed in the DNA structure. Nearly two-thirds of the direct read-out of DNA sequences involves complex networks of hydrogen bonds, which enhance specificity. Two-thirds of all protein-DNA interactions comprise van der Waals contacts, compared to about one-sixth each of hydrogen and water-mediated bonds. This highlights the central importance of these contacts for complex formation, which have previously been relegated to a secondary role. Although common, water-mediated bonds are usually non-specific, acting as space-fillers at the protein-DNA interface. In conclusion, the majority of amino acid-base interactions observed follow general principles that apply across all protein-DNA complexes, although there are individual exceptions. Therefore, we distinguish between interactions whose specificities are 'universal' and 'context-dependent'. An interactive Web-based atlas of side chain-base contacts provides access to the collected data, including analyses and visualisation of the three-dimensional geometry of the interactions.
authors: Biomolecular Structures and Modelling Unit, Department of Biochemistry and Molecular Biology, University College, Gower Street, London WC1E 6BT, UK.
authors: N M
authors: NM
authors: Luscombe
authors: R A
authors: RA
authors: Laskowski
authors: J M
authors: JM
authors: Thornton
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019992:Databases as Topic; D006860:Hydrogen Bonding; D020407:Internet; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012984:Software; D055672:Static Electricity; D013379:Substrate Specificity; D014867:Water / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014867:Water; D004247:DNA