Table 2.
Kinetic analysis of wildtype and variant ketosteroid reductases active against exemestane.
| Reductase enzyme or variant |
NCBI dbSNP Identifier |
1000 Genomes Project (MAF) |
GO-ESP (MAF) |
KM (µM) |
VMAX (picomoles·min−1·mg−1)a |
CLINT (nl·min−1·mg−1) |
|---|---|---|---|---|---|---|
| AKR1C1 | 35.3 ± 3.8 | 71.1 ± 1.5 | 2.0 | |||
| AKR1C2 | 16.4 ± 0.6 | 84.2 ± 15.6 | 5.1 | |||
| AKR1C2 Phe46Tyr | rs2854482 | 0.0649 | 0.07 | 13.5 ± 2.8 | 105.1 ± 6.3 | 7.8 |
| AKR1C3 | 12.3 ± 1.1 | 83.3 ± 15.4 | 6.8 | |||
| AKR1C3 His5Gln | rs12529 | 0.4203 | 0.43 | 17.9 ± 2.9 | 3.8 ± 0.1* | 0.21 |
| AKR1C3 Glu77Gly | rs11551177 | 0.0367 | 0.0503 | 13.9 ± 2.2 | 1.9 ± 0.2* | 0.14 |
| AKR1C3 Lys104Asn | rs12387 | 0.1518 | 0.1569 | 16.8 ± 1.0 | 6.4 ± 0.3* | 0.38 |
| AKR1C3 Pro180Ser | rs34186955 | 0.0086 | 0.0117 | 11.2 ± 3.1 | 3.6 ± 0.6* | 0.32 |
| AKR1C3 Arg258Cys | rs62621365 | 0.0325 | 0.001 | 75.8 ± 19.9* | 2.3 ± 0.1* | 0.03 |
| AKR1C4 | 9.7 ± 1.9 | 2.3 ± 0.6 | 0.24 | |||
| AKR1C4 Gly135Glu | rs11253043 | 0.027 | 0.0278 | 311.4 ± 75.7* | 19.1 ± 4.2* | 0.06 |
| AKR1C4 Ser145Cys | rs3829125 | 0.1028 | 0.1143 | 9.6 ± 2.4 | 5.9 ± 1.1 | 0.61 |
| AKR1C4 Leu311Val | rs17134592 | 0.1024 | 0.1143 | 11.9 ± 2.0 | 6.3 ± 0.8 | 0.53 |
| CBR1 | 265 ± 21 | 928 ± 244 | 3.50 |
a
All VMAX values were normalized to reflect the purity of recombinant enzymes assayed.
*
Denotes that a variant exhibited statistically significant deviations (p<0.001 in all cases) from the activity of its respective wildtype.