A ROLE FOR CH-CENTER-DOT-CENTER-DOT-CENTER-DOT-O INTERACTIONS IN PROTEIN-DNA RECOGNITION

The concept of CH ... O hydrogen bonds has recently gained much intere st, with a number of reports indicating the significance of these non- classical hydrogen bonds in stabilizing nucleic acid and protein struc tures. Here, we analyze the CH ... O interactions in the protein-DNA i nterface, based on 43 crystal structures of protein-DNA complexes. Sur prisingly, we find that the number of close intermolecular CH ... O co ntacts involving the thymine methyl group and position C5 of cytosine is comparable to the number of protein-DNA hydrogen bonds involving ni trogen and oxygen atoms as donors and acceptors. A comprehensive analy sis of the geometries of these close contacts shows that they are simi lar to other CH ... O interactions found in proteins and small molecul es, as well as to classical NH ... O hydrogen bonds. Thus, we suggest that C5 of cytosine and C5-Met of thymine form relatively weak CH ... O hydrogen bonds with Asp, Asn, Glu, Gin, Ser, and Thr, contributing t o the specificity of recognition. Including these interactions, in add ition to the classical protein-DNA hydrogen bonds, enables the extract ion of simple structural principles for amino acid-base recognition co nsistent with electrostatic considerations. (C) 1998 Academic Press Li mited.