Fig. 6. Kinetic model of DNA polymerase catalysis.

Proposed kinetic model during DNA polymerase correct nucleotide incorporation (a) and misincorporation (b). During correct nucleotide incorporation, the primer 3′-OH is well-aligned by the Me²⁺_A, and the reaction proceeds right after Me²⁺_C binding. In contrast, during incorrect nucleotide incorporation, due to reduced base-stacking, primer 3′-OH alignment is unfavored, which would lead to incorrect dNTP dissociation. Error-prone Mn²⁺_A can drive 3′-OH alignment and once the Me²⁺_C binds, catalysis ensues.