Table 2.
Substrate1 | AcCYP51 | SMT5 | |||
---|---|---|---|---|---|
Kd (μM)2 | AfCPR kcat (min−1)3 | 24-SMT kcat(min−1) | 28-SMT kcat(min−1) | ||
10 | 4α, 14α-Dimethylergosta-8,24(28)-dienol | 41 ±3 | 7.6 ±0.05 | 0 | 0 |
32 | Lanosta-8,24(28)-dienol | 51 ±10 | 3.2 ±0.04 | nd | nd |
33 | Lanosta-8,24(25)-dienol | 46 ±3 | 1.7 ±0.01 | 1.50 ±0.01 | 0.23 ±0.01 |
34 | Lanost-8-enol | 60±12 | 2.0 ±0.002 | nd | nd |
35 | 14α-Methylcholest-8,24(25)-dienol | 12 ±2 | 1.6 ±0.08 | 1.50 ±0.05 | 0.39 ±0.02 |
24 | 4α-Methylcycloart-24(28)-enol | No fit | 0.04 ±0.01 | nd | nd |
21 | Cycloart-24(25)-enol | 18 ±5 | 0 | 1.50 ±0.07 | 0.45 ± 0.03 |
27 | Cycloart-24(28)-enol | No fit | 0 | 0 | 0.23 ±0.05 |
36 | Lanosta-7,24(25)-dienol | Nd4 | 0 | nd | nd |
37 | 4α, 14α-Dimethyl cholesta-8,24(25)-dienol | nd | 0 | 1.50 ±0.04 | 0.74 ±0.02 |
14 | 4α-Methylergosta-7,24(28)-dienol | nd | 0 | 0 | 0.80 ± 0.04 |
See supplemental Figure 3 for a key to structures;
Kd value was determined by progressive titration of 4 M AcCYP51 with sterol in 40% (W/V) HPCP;
kcat was determined in the CYP51 reconstitution assays for 50 μM sterol using AfCPR redox partners;
nd, not determined;
Kinetic constants for SMT were determined previously for these sterols assayed in the range 5 μM to 150 μM against 150 μM SAM and 80 μg SMT as described in reference 33.