TABLE 1.
Kinetic parameters and sensitivity to 2093 inhibition of wild-type and mutant (T246I and D243E) CpMetRS enzymes
| Enzyme | Met titration |
ATP titration |
IC50 (nM) for 2093 | Ki (nM) for 2093 | ||||
|---|---|---|---|---|---|---|---|---|
| Km (μM) | kcat (s−1) | kcat /Km (μM−1 s−1) | Km (μM) | kcat (s−1) | kcat /Km(μM−1 s−1) | |||
| WT | 31.3 | 30.6 | 0.98 | 1,623 | 99.0 | 0.064 | 174.1 ± 23.3 (n = 2) | 0.0017 ± 0.0003 (n = 2) |
| T246I mutant | 2.93 | 116.8 | 39.8 | 410.3 | 111.2 | 0.271 | >10,000, >30,000 | >31.8, >99.9 |
| D243E mutant | 6.94 | 158.6 | 22.8 | 890.6 | 138.9 | 0.156 | >10,000, >30,000 | >33.3, >99.9 |