Table 3.
D2 nucleotide binding, kinetic properties, and IC50 values of CB-5083 and NMS-873 for p97 and the P472L mutant with R635A or R638A arginine finger mutations
Values shown are mean ± S.E. (n = 2, ATP and ADP binding; n = 4, activity).
| KD, ADP | KD, ATP | KM | kcat | kcat/KM | CB-5083 | NMS-873 | |
|---|---|---|---|---|---|---|---|
| μm | μm | μm | min−1 | (μm−1 min−1 × 10−3) | nm | nm | |
| WT | 0.6 ± 0.07 | 1.8 ± 0.2 | 77 ± 9 | 8.6 ± 0.3 | 112 ± 14 | 8.1 ± 0.8 | 12 ± 1 |
| R635A | 0.8 ± 0.1 | 4.6 ± 0.6 | 88 ± 11 | 0.29 ± 0.01 | 3.2 ± 0.4 | >8000a | >8000a |
| R638A | 1.2 ± 0.1 | 3.5 ± 0.4 | 48 ± 4 | 0.39 ± 0.01 | 8.1 ± 0.7 | >8000a | >8000a |
| P472L | 1.1 ± 0.1 | 0.4 ± 0.06 | 40 ± 5 | 37 ± 1 | 924 ± 114 | 118 ± 17 | 674 ± 58 |
| R635A | 0.9 ± 0.1 | 2.6 ± 0.2 | 29 ± 5 | 0.94 ± 0.04 | 32 ± 5 | 31 ± 4 | 72 ± 12 |
| R638A | 1.4 ± 0.1 | 4.0 ± 0.4 | 36 ± 3 | 1.14 ± 0.02 | 31 ± 3 | 79 ± 18 | 254 ± 29 |
a Activity inhibition was not observed over the concentration range tested.