DNA Polymerase: Structural Homology, Conformational Dynamics, and the Effects of Carcinogenic DNA Adducts
Figure 7
Two structures of Dpo4 ternary complexes in the presence of a dG-C8-AF adducted template, one forming a correctly aligned primer-template and a second forming a looped out structure of the template (PDB# 3KHH) [27]. (a) Correctly aligned primer template with the dGTP and corresponding template dC correctly at the 0 position. The adducted dG retains base paring with its corresponding dC while the AF is positioned towards the major groove and stacks in a pocket of the little fingers domain. The templating base stacks on top of the AF adduct and is in alignment with the 0 position. (b) The misaligned structure contains the templating base in a looped out structure. The looped out base slides into a pocket, rotated away from the active site. As a consequence the templating base rotates and stacks on top of the adducted dG base, and the DNA is shifted downwards as the base now occupies the position within the polymerase. The AF adduct is rotated downwards and placed into a hydrophobic pocket within the little fingers domain. The dGTP does not contain any Watson-Crick binding partner as it occupies the 0 position and stacks onto of the template base below.
