Sequence-specific recognition of double helical nucleic acids by proteins.

TLDR

Protein recognition of DNA base pairs is investigated by comparing base pair characteristics. The study proposes that two‑hydrogen‑bond side‑chain interactions form part of the base‑pair recognition system. The authors suggest that asparagine or glutamine side chains bind adenine in the major groove, arginine binds guanine, and in the minor groove asparagine or glutamine bind guanine, with ions and other residues also contributing to recognition. They find that a single hydrogen bond cannot uniquely identify a base pair, but two hydrogen bonds can achieve high‑fidelity recognition.

Abstract

The base pairs in double helical nucleic acids have been compared to see how they can be recognized by proteins. We conclude that a single hydrogen bond is inadequate for uniquely identifying any particular base pair, as this leads to numerous degeneracies. However, using two hydrogen bonds, fidelity of base pair recognition may be achieved. We propose specific amino-acid side chain interactions involving two hydrogen bonds as a component of the recognition system for base pairs. In the major groove we suggest that asparagine or glutamine binds to adenine of the base pair or arginine binds to guanine. In the minor groove, we suggest an interaction between asparagine or glutamine with guanine of the base pair. We also discuss the role that ions and other amino-acid side chains may play in recognition interactions.