Table 1. Complementary dNTP or rNTP Binding Rates for Wild-Type Φ29 DNAP and Mutantsa.
enzyme | DNA | ligand | kon (s–1 μM–1)b | koff (s–1)c | koff (s–1)/kon (s–1 μM–1) | Kd (μM)d |
---|---|---|---|---|---|---|
wt | DNA1-H_H | dGTP | 21.4 ± 0.6 | 31.9 ± 0.5 | 1.49 ± 0.03 | 1.31 ± 0.04 |
Y254V | DNA1-H_H | dGTP | 19.7 ± 0.9 | 140 ± 4 | 7.3 ± 0.3 | 6.59 ± 0.2 |
D12A/D66A | DNA1-H_H | dGTP | 16.7 ± 0.4 | 17.7 ± 0.3 | 1.02 ± 0.02 | 0.99 ± 0.04 |
D12A/D66A/Y254V | DNA1-H_H | dGTP | 32.4 ± 1.0 | 126 ± 2.3 | 3.9 ± 0.2 | 4.76 ± 0.17 |
wt | DNA1-H_H | rGTP | >3.2 | >5400 | e | 1702 ± 239 |
Y254V | DNA1-H_H | rGTP | 8.9 ± 1.8 | 777 ± 16 | 91 ± 24 | 83.6 ± 3.6 |
D12A/D66A | DNA1-H_H | rGTP | >7.1 | >4900 | e | 695 ± 32 |
D12A/D66A/Y254V | DNA1-H_H | rGTP | 12.6 ± 1.9 | 546 ± 32 | 45.2 ± 4.2 | 53.1 ± 1.6 |
wt | DNA1-OH_H | dGTP | 8.9 ± 1.8 | 526 ± 28 | 60.8 ± 9.1 | 59.4 ± 7.3 |
Y254V | DNA1-OH_H | dGTP | 12.7 ± 0.3 | 1126 ± 39 | 85.7 ± 1.8 | 86.4 ± 6.1 |
D12A/D66A | DNA1-OH_H | dGTP | 9.9 ± 0.6 | 318 ± 26 | 32 ± 1.0 | 27.2 ± 1.7 |
D12A/D66A/Y254V | DNA1-OH_H | dGTP | 14.8 ± 0.2 | 897 ± 19 | 58.8 ± 1.3 | 63.4 ± 2.6 |
Rates were determined using dwell time samples extracted from ionic current traces (see Methods section) and a three-state kinetic model (consisting of transitions r1, r2, kon and koff in the model diagram in Figure 1a). Experiments were conducted at 180 mV; kon[dNTP] and koff are independent of the applied voltage.38 All values are reported with the standard error.
The dNTP or rNTP association rate constant.
The dNTP or rNTP dissociation rate.
Kd values are determined from the vertical intercepts of the fitting lines to the log–log plot of normalized p/(1 – p) – 1 vs [dGTP] or [rGTP], where p is equilibrium probability of the lower amplitude level (see the model diagram in Figure 1a). The plots of normalized p/(1 – p) – 1 vs [dGTP] or [rGTP] are shown in Figures 5 and 7.
Not determined.