Protein-DNA interactions: A structural analysis

A detailed analysis of the DNA-binding sites of 26 proteins is presented us ing data from the Nucleic Acid Database (NDB) and the Protein Data Bank (PD B). Chemical and physical properties of the protein-DNA interface, such as polarity, size, shape, and packing, were analysed. The DNA-binding sites sh ared common features, comprising many discontinuous sequence segments formi ng hydrophilic surfaces capable of direct and water-mediated hydrogen bonds . These interface sites were compared to those of protein-protein binding s ites, revealing them to be more polar, with many more intermolecular hydrog en bonds and buried water molecules than the protein-protein interface site s. By looking at the number and positioning of protein residue-DNA base int eractions in a series of interaction footprints, three modes of DNA binding were identified (single-headed, double-headed and enveloping). Six of the eight enzymes in the data set bound in the enveloping mode, with the protei n presenting a large interface area effectively wrapped around the DNA. A comparison of structural parameters of the DNA revealed that some values for the bound DNA (including twist, slide and roll) were intermediate of th ose observed for the unbound B-DNA and A-DNA. The distortion of bound DNA w as evaluated by calculating a root-mean-square deviation on fitting to a ca nonical B-DNA structure. Major distortions were commonly caused by specific kinks in the DNA sequence, some resulting in the overall bending of the he lix. The helix bending affected the dimensions of the grooves in the DNA, a llowing the binding of protein elements that would otherwise be unable to m ake contact. From this structural analysis a preliminary set of rules that govern the bending of the DNA in protein-DNA complexes, are proposed. (C) 1 999 Academic Press.