Studies of protein-nucleic acid interactions using model crystals.

For the mutual recognition between protein and nucleic acid, specific interactions between the components of both polymers should be properly combined in a fitting scheme of secondary or tertiary structures. We call these combinations elementary interactions between protein and nucleic acid. The interactions were investigated using the model crystals that contain side chains of amino acid and a nucleic acid base. Taking C, T, U, A, and G as base and hydroxyl, carboxyl, carbamoyl, imidazolyl, phenyl, hydroxyphenyl, and indolyl groups as side chains of amino acid, several combinations were extensively studied. Interaction patterns between complementary base pairs and amino acids were also examined using ternary model systems. Several characteristics are observed in the model crystals, for instance, stabilization of stacking between the bases and histidine by the protonation of the latter, common hydrogen bonding patterns between bases and a hydroxyl or carboxyl group by reversal of donor-acceptor relationship or ionization. UV, NMR experiments and calculation by molecular orbital methods revealed energetic aspects of these interactions. A structural constraint is derived between the hydrogen bonds and the secondary structural fitting of an alpha-helical segment into the major groove of B-DNA. In terms of elementary interactions, stereochemical interpretations are given for the selectivity and enzymatic reaction of RNAase, binding of cro repressor to operator and initiation and elongation in the assembly of tobacco mosaic virus.