Ki values from serotonin and dopamine uptake inhibition experiments in wild-type hDAT, wild-type hSERT, and mutants
Confidence levels are provided in Supplemental Table 4. Residues Val343, Thr439, Leu443, and possibly Asn177 are suggested by S-C1 to interact with the 4′-substituent on mazindol, whereas A173, and possibly Ile165 are suggested by R-C1 to interact with the 4′-substituent on mazindol. Ala169 is located between the 4′-substituent on mazindol in R-C1 and S-C1.
| Transporter Variant | Mazindol | Analog | |||
|---|---|---|---|---|---|
| 5 | 6 | 7 | 8 | ||
| nM | |||||
| Wild-type hSERT | 0.48 | 5.4 | 1.92 | 12.3 | 21 |
| hSERT N177A | 0.073 | 0.150 | 0.39 | 2.7 | ND |
| hSERT N177S | 0.035 | 0.27 | 0.26 | 6.7 | 3.0 |
| hSERT N177T | 0.028 | 0.20 | 0.22 | 5.0 | 4.6 |
| hSERT N177Q | ND | ND | 1.43 | 5.9 | 13.6 |
| hSERT T439A | 1.24 | 2.5 | 0.94 | 3.4 | 5.1 |
| hSERT T439S | 0.92 | 1.34 | 0.31 | 2.44 | 4.3 |
| hSERT T439V | 0.24 | 2.1 | 0.87 | 3.5 | 5.4 |
| hSERT L443S | 1.05 | 4.5 | 1.11 | 5.3 | 8.3 |
| hSERT A169S | 0.48 | 4.8 | 3.4 | 3.6 | 27 |
| hSERT I165A | 0.144 | 1.72 | 0.72 | 0.58 | 6.6 |
| hSERT I165S | 0.145 | 2.0 | 1.08 | 3.1 | 9.0 |
| hSERT I165T | 0.182 | 1.72 | 0.77 | 2.2 | 4.4 |
| hSERT I165N | 0.183 | 2.8 | 0.70 | 2.2 | 17.2 |
| hSERT A173S | 0.32 | 1.54 | 1.41 | 12.1 | 15.9 |
| hSERT A173L | 0.0132 | 0.062 | 0.035 | 0.47 | 0.55 |
| hSERT A173M | ND | ND | ND | ND | 0.94 |
| hSERT V343S | 0.49 | 8.4 | 3.1 | 11.5 | 28 |
| Wild-type hDAT | 0.140 | 1.27 | 3.8 | 35.5 | 14.5 |
ND, not determined.