Amino acid side chains determine the specificity of DNA bindingInteractions between amino acids and bases determine the specificity and affinity of DNA-binding proteins. The amino acid sequences of the recognition helices of the λ repressor and Cro proteins are shown. Interactions between the glutamine (Gln), serine (Ser), and alanine (Ala) residues of the λ repressor and bases in the OR operator determine the strength of binding. Similarly, interactions between the glutamine, serine, asparagine (Asn), and lysine (Lys) residues of the Cro protein mediate binding to the OR3 operator. Each DNA sequence shown is that bound by an individual monomer of the respective repressor; it is half of the operator site occupied by the repressor dimer.
[Data from M. Ptashne, A Genetic Switch: Phage l and Higher Organisms, 2nd ed.]