Extended Data Fig. 7: Definition of rate constants in the kinetic mechanism used to model misincorporation.
From: Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs
Shown are kinetic mechanisms for (A) correct dA•dTTP Watson-Crick incorporation. (B) dA•dGTP misincorporation and (C) dA•d8OGTP misincorporation. In (B), k1, k-1(dNTP), k3, and k-3 are used in Models 1, 2, and 1 + 2. In Model 1, only Aanti+•Gsyn is accepted as the mutagenic intermediate and can proceed forward with rate constants k2 and k-2 while Asyn•Ganti can be unbound by the polymerase with rate constants k1 and k-1(ES1). Model 2 is the same as Model 1 but with Asyn•Ganti as the mutagenic form proceeding forward with rate constants k2 and k-2 and Aanti+•Gsyn unbound with rate constants k1 and k-1(ES2). In Model 1 + 2, both Aanti+•Gsyn and Asyn•Ganti can proceed forward with misincorporation with rate constants k2 and k-2. Neither ES species can unbind. (C) Kinetic mechanism of dA•d8OGTP misincorporation. All rate constants listed are used. E, Eʹʹ, Eʹ, and E* refer to DNA polymerase in the open, ajar, closed, and catalytically active conformations, respectively.
