TABLE 5.
Molecular interactions of DM490, DM497, and PAM-4 at the subunit interfaces and ion channel of the α1β2γ2 GABAAR model
| DM490 | DM497 | PAM-4 | ||||
|---|---|---|---|---|---|---|
| Intersubunit Sites | ||||||
| Docking Site | (+) side | (−) side | (+) side | (−) side | (+) side | (−) side |
| β/α (A) | TM2: M261 T262 N265 TM3: L285 M286 F289 V290 |
TM1: I228 Q229 L232 P233 M236 |
TM2: T262 N265 TM3: D282 L285 M286 F289 V290 |
TM1: I228 Q229 L232 P233 M236 |
TM2: M261 T262 N265 TM3: L285 M286 F289 V290 |
TM1: I228 N229 L232 P233 M236 |
| α/β (A) | TM2: T267 S270 TM3:A283 D287 W288 I290 A291 Y294 |
TM1: L223 M227 P228 L231 |
Near stable | Near stable | ||
| γ/β (A) | Near stable | TM2: T277 S280 TM3: S301 F304 I305 F308 |
TM1: L223 Q224 M227 P228 L231 |
Near stable | ||
| α/γ (O) | Unstable | TM2: S270 TM3: D287 I290 A291 Y294 A295 F298 S299 I302 |
TM1: I238 I242 L246 |
Near stable | ||
| Ion Channel Site | ||||||
| γ subunit | Not found | Not found | TM2: L274 (9’), T277, T278 (13’) | |||
| β subunit | Near stable | Unstable | TM1: I232 TM2: I255, T256, L259 (9’), T260, T263 (13’), I264 |
|||
| α subunit | TM2: T261 (6’), T265 | |||||
A, anesthetic site; O, orphan site.
The “+” and “−” sides indicate contributions made by the two sides of an intersubunit interface within a counterclockwise order of subunits.
Residues in bold: π-π interactions.
Residues at 6’, 9’, and 13’ correspond to the canonical TM2 rings in the ion channel lumen.