Table 1. Summary of Pre-Steady-State Kinetic Parameters and Functional Consequences of Various RB69pol Variants.
subdomain | residue | functional interactions with RB69pol | amino acid substitution | kpol (s–1) or kexo (s–1)a | Kd (μM) | kpol/Kd (μM–1 s–1) | ref |
---|---|---|---|---|---|---|---|
palm | Y391 | HB to Y567, HB network at minor groove | Y → A | 155 | 980 | 1.5 × 10–1 | (60) |
Y → F | 312 | 90 | 3.5 | ||||
D411 | ligands to metal ion at pol site | D → A | inactive | (53) | |||
L415 | HB to β-phosphate of the incoming dNTP | L → A | 11 | 3 | 3.7 | (82) | |
L → G | 58 | 9 | 6.4 | ||||
L → M | 375 | 12 | 31.3 | ||||
Y416 | “sugar gate”, sterically blocks the 2′-OH group of an incoming rNTP | Y → A | 22 | 70 | 3.1 × 10–1 | (54) | |
Y → F | 36 | 209 | 1.7 × 10–1 | ||||
T587 | HB to Y567, HB network at minor groove | T → A | 0.8 | 0.7 | 1.1 × 10–1 | (60) | |
Y619 | HB to a water molecule, HB network at minor groove | Y → F | 14 | NDb | NDb | (53) | |
D621 | HB to K706, HB network at the minor groove | D → A | 1.3 | 166 | 7.8 × 10–3 | (53) | |
T622 | HB to D621, anchors the side chain of D623 | T → A | 0.2 | NDb | NDb | (53) | |
D623 | ligands to metal ion at pol site | D → A | inactive | (53) | |||
S624 | ligands to metal ion at pol site via a water molecule | S → C | 4.5 | 18 | 2.5 × 10–1 | (53) | |
E686 | ligands to metal ion at pol site via a water molecule | E → A | 7 | 58 | 1.2 × 10–1 | (53) | |
K706 | HB to D621 and base at position n – 2 of primer strand | K → R | 0.1 | NDb | NDb | (53) | |
fingers | R482 | HB to γ-phosphate of the incoming dNTP | R → A | 0.2 | 1100 | 1.8 × 10–4 | (58) |
K486 | HB to γ-phosphate of dNTP via a water molecule | K → A | 3.3 | 71 | 4.6 × 10–2 | (58) | |
K560 | HB to α,γ-phosphate of the incoming dNTP | K → A | 0.8 | 790 | 1.0 × 10–3 | (58) | |
L561 | anchoring the templating base at the major groove | L → A | 101 | 50 | 2.0 | (61) | |
N564 | HB to β-phosphate of dNTP | N → A | 23 | 250 | 9.2 × 10–2 | (58) | |
S565 | anchoring the templating base | S → G | 157 | 48 | 3.3 | (76) | |
Y567 | HB to Y391, HB network at minor groove | Y → A | 213 | 68 | 3.1 | (60) | |
Y → F | 7.5 | 2400 | 3.1 × 10–3 | ||||
thumb | Y708 | HB to 3′-terminal phosphodiester bond (primer strand) | Y → A | 6 | 34 | 1.8 × 10–1 | (53) |
E716 | ligands to a third metal ion at the pol site | E → A | 200 | NDb | NDb | (53) | |
exonuclease | E116 | ligands to metal ion at the exo site | E → A | 2.8 × 10–4a | (42) | ||
D222 | ligands to metal ion at the exo site | D → A | inactivea | (42) | |||
K302 | anchors the side chain of D327 | K → A | 1.0 × 10–2a | (42) | |||
Y323 | HB to Q171, anchors the backbone of D327 | Y → F | 5.8 × 10–3a | (42) | |||
D327 | ligands to metal ion at the exo site | D → A | inactivea | (42) |
Indicates the excision rate for RB69pol variants.
Not determined.