Table 1 I3:PP1 binding and inhibition
From: Inhibitor-3 inhibits Protein Phosphatase 1 via a metal binding dynamic protein–protein interaction
PP1 and I3 variants | Binding | Inhibition | |||
|---|---|---|---|---|---|
PP17-330 vs I3 variants | KD (nM) | Fit | n | IC50 (nM) | n |
I31-126 (FL, full-length) | |||||
I31-126 | 15.7 ± 2 | 2 | 3 | 71 ± 6 | 3 |
SILKdead: I31-126 T29A/I30A/K31A | 13.1 ± 2.8 | 2 | 3 | nd | nd |
RVxFdead: I31-126 40KAEA43 | 3460 ± 531 | 1 | 4 | nd | nd |
SSS: I31-126 C60S/C61S/C62S | 300 ± 23 | 1 | 3 | nd | nd |
I327-68 (I3 PP1 interaction domain) | |||||
pH = 8.0 | 9.3 ± 1.1 | 2 | 4 | 75 ± 4 | 8 |
pH = 7.5 | 9 ± 0.6 | 2 | 3 | nd | nd |
pH = 7.0 | 16.1 ± 1.1 | 2 | 3 | nd | nd |
pH = 6.5 | 17 ± 0.8 | 2 | 3 | nd | nd |
SILKdead: I327-68 T29A/I30A/K31A | 16.8 ± 2.8 | 2 | 3 | nd | nd |
SCC: I327-68 C60S | 21.7 ± 3.1 | 2 | 5 | 243 ± 13 | 4 |
CSC: I327-68 C61S | 18.8 ± 0.9 | 2 | 3 | 158 ± 13 | 4 |
CCS: I327-68 C62S | 20.6 ± 5.1 | 2 | 3 | 171 ± 7 | 4 |
CSS: I327-68 C61S/C62S | 21.2 ± 0.6 | 2 | 2 | 153 ± 10 | 4 |
SCS: I327-68 C60S/C62S | 54 ± 9 | 2 | 3 | 179 ± 15 | 4 |
SSC: I327-68 C60S/C61S | 86.8 ± 3.8 | 1 | 4 | 349 ± 19 | 4 |
SSS: I327-68 C60S/C61S/C62S | 412 ± 6 | 1 | 3 | 380 ± 31 | 4 |
IY: I327-68 I63A/Y64A | 15.6 ± 2.4 | 2 | 3 | nd | nd |
I327-68 deletion variants | |||||
SILKdeletion: I338-68 (Δ27-37) | 15.2 ± 2.5 | 2 | 3 | nd | nd |
CCCdeletion: I327-59 (Δ60-68) | 376 ± 47 | 1 | 3 | 422 ± 113 | 4 |
I379-91 | |||||
I379-91 | No binding | 3 | nd | nd | |
I327–68 vs. different PP1 variants | |||||
PP17–330 C273S | 16.1 ± 0.7 | 2 | 3 | 85 ± 3 | 8 |
PP17–330 H66K | 5.9 ± 0.6 | 2 | 2 | nd | nd |
PP17–330 H248N | 6.6 ± 1.7 | 2 | 2 | nd | nd |
