Table 1.
Mutations in residues that are identical or similar in StAR and MLN64 cause loss of steroidogenic activity in human StAR
| Mutation | Residue type | Relative steroidogenic activity |
|---|---|---|
| S100A | N | 86 ± 5 |
| E169G | S | 13 ± 1* |
| E169K | S | 14 ± 2* |
| R182L | Id | 11 ± 1* |
| D183A | Id | 44 ± 5 |
| F184C | Id | 56 ± 6 |
| T196A | N | 119 ± 18 |
| A218V | S | 16 ± 4* |
| M225T | S | 49 ± 9‡ |
| D246A | Id | 63 ± 8 |
| K248M | Id | 51 ± 3 |
| F267Y | Id | 65 ± 1 |
| H270Y | Id | 81 ± 7 |
| ΔR272 | Id | 11 ± 1* |
| L275P | S | 24 ± 5* |
| S277A | N | 90 ± 16 |
| C285S | N | 105 ± 11† |
| ΔC285 | N | 110 ± 8† |
| ΔS282, ΔE283, ΔR284, ΔC285 | N | 102 ± 7† |
| Empty plasmid | 14 ± 2 |
COS-1 cells were transfected with the human cholesterol side-chain cleavage system, and expression plasmids for wild-type StAR, the indicated mutations, or empty plasmid. Steroidogenic activity was assessed by measuring pregnenolone production and is expressed relative to wild-type StAR as 100% normalized to (22R)-22-hydroxycholesterol metabolism as previously described (4). Id, identical; N, not conserved; S, similar. The footnote symbols indicate results taken from our previous publications: ∗, ref. 4; †, ref. 5; and ‡, ref. 10. All other values represent newly created mutations. Values are means ± SE from at least three separate experiments.