Figure 6.

Overlays of crystal structures of ternary hPol η complexes with all-DNA or TNA-modified template strands with thymine or O⁴-Me or -Et adducted thymine nucleobases. (A) Comparison between insertion complexes featuring either template tT⁴ (yellow carbons, this work) or dT⁴ (gray carbons, PDB ID 3MR2(42)) opposite incoming dAMPnPP. (B) Comparison between insertion complexes featuring either template dT⁴ (gray carbons, PDB ID 3MR2) or O⁴-Me dT⁴ (magenta carbons, PDB ID 5DLF(41)) opposite incoming dAMPnPP. (C) Comparison between insertion complexes featuring O⁴-Me tT⁴ (yellow carbons, in this work) or O⁴-Me dT⁴ (magenta carbons, PDB ID 5DLF) opposite incoming dAMPnPP. (D) Comparison between extension complexes featuring O⁴-Me tT⁵ (yellow carbons, this work) or O⁴-Et dT⁵ (light blue, PDB ID 5DQI(41)) paired opposite primer dA⁸ at the −1 postreplicative position and wedged between the replicating dG⁴:dCMPnPP (dCTP) and −2 position dT⁶:dA⁷ base pairs. (E) Comparison between ternary complexes of hPol η with incoming dTTP (light pink carbons, PDB ID 6PL7) and tTTP (yellow carbons, this work) opposite dA⁴ in the DNA template-primer duplex. (F) Comparison between ternary complexes of hPol η with incoming rCTP opposite dG⁴ (cyan carbons, PDB ID 5EWE(57)) or tTTP opposite dA⁴ (yellow carbons, this work). Coordinated Mg²⁺ and Ca²⁺ ions are depicted as cyan and pink spheres, respectively, in all of the figure panels. (G) Active-site view illustrating differences in the orientations of 2′-deoxyribose and threose sugar rings with respect to the Phe18 (steric gate) and Tyr92 (second line of defense) hPol η residues in the structures of complexes with dA:dTMPnPP (light pink carbons, PDB ID 6PL7) or dATP:tTTP (yellow carbons, this work), respectively. (H) Active-site view illustrating differences in the orientations of ribose and threose sugar rings with respect to the Phe18 and Tyr92 in the structures of complexes with dG:rCTP/dA:rCTP (cyan carbons, PDB ID 5EWE/6PL7⁵⁷) or dA:tTTP (yellow carbons, this work), respectively.