Mutation | MPEP | VU0360172 (Nicotinamide) | VU0403602 (Picolinamide) | VU0360173 (Nicotinamide) | VU0405398 (Picolinamide) | VU0415051 (Nicotinamide) | VU0405386 (Picolinamide) |
---|---|---|---|---|---|---|---|
R5-wt (poly) | 8.58 ± 0.17# | 6.68 ± 0.15 | 8.13 ± 0.26 | 5.45 ± 0.27 | 6.94 ± 0.17 | 7.34 ± 0.18 | 8.04 ± 0.26 |
R647A | 8.89 ± 0.19 | 6.29 ± 0.12 | 7.99 ± 0.09 | 4.91 ± 0.14 | 6.94 ± 0.10 | 7.28 ± 0.25 | 7.74 ± 0.12 |
I650A | 8.62 ± 0.03 | 7.12 ± 0.19 | 7.97 ± 0.13 | N.D. | 7.29 ± 0.15 | N.D. | 8.10 ± 0.15 |
G651F | 7.53 ± 0.18* | 5.86 ± 0.18* | 6.50 ± 0.18* | No PAM | 5.99 ± 0.28* | 6.94 ± 0.19 | 7.14 ± 0.08 |
P654S | 7.10 ± 0.06* | 6.39 ± 0.24 | 7.33 ± 0.16 | <5 | 5.80 ± 0.27* | 5.69 ± 0.46* | 7.81 ± 0.27 |
P654F | 4.11 ± 0.21* | 5.91 ± 0.17 | 5.99 ± 0.26* | No PAM | 5.33 ± 0.27* | 5.25 ± 0.19* | 6.23 ± 0.22* |
S657C | 8.32 ± 0.08 | N.D. | 7.41 ± 0.17 | N.D. | 6.99 ± 0.31 | 6.78 ± 0.12 | 7.68 ± 0.06 |
Y658V | 6.57 ± 0.13*# | No PAM | No PAM | No PAM | 4.97 ± 0.35* | No PAM | No PAM |
P742S | 8.07 ± 0.17* | 6.57 ± 0.10 | 7.50 ± 0.12 | 4.65 ± 0.17 | 6.83 ± 0.20 | 7.09 ± 0.04 | 7.96 ± 0.16 |
L743V | 8.04 ± 0.10*# | 6.97 ± 0.15 | 7.93 ± 0.14 | 5.46 ± 0.12 | 6.77 ± 0.11 | 7.75 ± 0.20 | 8.36 ± 0.10 |
N746A | 8.30 ± 0.06 | 6.66 ± 0.10 | 7.99 ± 0.11 | N.D. | 6.50 ± 0.23 | N.D. | 8.06 ± 0.17 |
T780A | 7.36 ± 0.02* | No PAM | 6.03 ± 0.13* | No PAM | 5.59 ± 0.05* | 5.82 ± 0.40* | 5.32 ± 0.24* |
W784A | 5.50 ± 0.29* | 6.76 ± 0.14 | 7.09 ± 0.34* | 5.03 ± 0.44 | 6.23 ± 0.20 | 7.14 ± 0.15 | 7.53 ± 0.14 |
V788A | 7.89 ± 0.13* | 7.28 ± 0.17 | 8.43 ± 0.20 | 6.28 ± 0.18 | 7.84 ± 0.14 | 8.07 ± 0.19 | 8.79 ± 0.08 |
F792A | 8.93 ± 0.04 | 7.25 ± 0.33 | 8.03 ± 0.02 | 4.80 ± 0.20 | 7.34 ± 0.20 | 8.06 ± 0.24 | 7.02 ± 0.47* |
S806A | 8.36 ± 0.06 | N.D. | N.D. | N.D. | N.D. | N.D. | 7.29 ± 0.45 |
S808A | 6.98 ± 0.18* | 6.15 ± 0.30 | 6.47 ± 0.10* | No PAM | 6.28 ± 0.09 | 7.20 ± 0.44 | 7.48 ± 0.20 |
S808T | 6.90 ± 0.06* | 6.59 ± 0.20 | 7.15 ± 0.33* | 5.04 ± 0.33 | 6.40 ± 0.23 | 6.36 ± 0.26* | 8.05 ± 0.27 |
A809V | 6.52 ± 0.12*# | 5.64 ± 0.19* | 6.52 ± 0.21* | No PAM | No PAM | 5.56 ± 0.12* | 6.22 ± 0.14* |
A809G | 7.18 ± 0.04* | 5.93 ± 0.18 | 6.59 ± 0.05* | 5.13 ± 0.13 | 5.88 ± 0.05* | 6.28 ± 0.11* | 6.60 ± 0.24* |
C815A | 8.35 ± 0.05 | 6.58 ± 0.22 | 7.29 ± 0.26* | 4.81 ± 0.13 | 6.73 ± 0.35 | 7.26 ± 0.11 | 7.63 ± 0.15 |
N.D., not determined; No PAM, no observed positive allosteric modulation.
↵* P < 0.05 vs. wild-type value, one-way analysis of variance (ANOVA), Dunnett’s post-test; #data previously reported (Gregory et al., 2012).