Whether the amino–imino tautomerism of 2-aminopurine is involved into its mutagenicity? Results of a thorough QM investigation

Abstract

The biologically important issue of whether the amino–imino tautomerism of 2-aminopurine (2AP) is the cause of the replication and incorporation point errors induced by this mutagen, has been debated for a long time in the literature. Exploring by quantum-mechanical methods the ability of the irregular pairs formed by the H-bonding of the imino tautomer of the 2-aminopurine (2AP*) with canonical DNA bases to acquire enzymatically-competent conformation that guarantees their successful incorporation into the structure of the DNA double helix by the high-fidelity DNA-polymerase, we came to the conclusion that 2AP tautomerism is not implicated into the origin of the replication point errors induced by this mutagen. We have authentically established that 2AP* mutagenic tautomer is able to induce only one single incorporation mistake, namely transversion, by pairing through the two N1H⋯O6 and N1H⋯N2 H-bonds with guanine (G) DNA base into the wobble (w) G·2AP*(w) pair. At this, the formed pair acquires enzymatically-competent Watson–Crick (WC) conformation by following the pathway of the tautomeric and conformational transformations G·2AP*(w) → G*·2AP(w) → G·2AP(WC) → G·2AP_syn → G·2AP_syn(WC). In this case, the long G·2AP(WC) wrong pair, stabilized by the participation of the three C6H⋯O6, N1H⋯N1 and N2H⋯N2 H-bonds, acts as a predecessor of the enzymatically-competent conformation – the G·2AP_syn(WC) mispair.