Structural determinants of PYD modulation
Response as a percent of control are shown for 100 μM PYD-1 coapplied with 100 μM glutamate and 30 μM glycine.
| GluN2C Mutation | ITEST/ICONTROL | n | GluN2C Mutation | ITEST/ICONTROL | n |
|---|---|---|---|---|---|
| % | % | ||||
| Wild type | 247 ± 2.3 | 63 | P428R# | 208 ± 6.0* | 8 |
| R194D# | 112 ± 1.1* | 8 | N429D# | 182 ± 8.0* | 5 |
| E341D | 217 ± 4.7 | 4 | T430S# | 203 ± 3.2* | 7 |
| G342N | 259 ± 4.2 | 4 | R435K | 244 ± 3.8 | 5 |
| F345L | 262 ± 1.4 | 3 | Q436F | 244 ± 8.1 | 6 |
| M371V | 263 ± 5.4 | 7 | S437V | 274 ± 16 | 4 |
| R374S | 267 ± 5.7 | 6 | N438F | 244 ± 9.5 | 5 |
| D376E | 239 ± 6.1 | 8 | H439I | 258 ± 3.9 | 8 |
| H377N | 276 ± 7.9* | 6 | T440N | 242 ± 4.7 | 3 |
| G378Q | 238 ± 7.2 | 6 | F441N | 250 ± 4.0 | 5 |
| V379T | 229 ± 9.9 | 6 | S443T | 262 ± 6.7 | 6 |
| Y381S | 263 ± 11.2 | 6 | G444N | 238 ± 7.7 | 8 |
| M382L | 242 ± 5.4 | 4 | D445N | 259 ± 6.2 | 6 |
| K383R | 217 ± 6.9* | 6 | L446E | 242 ± 6.5 | 6 |
| S391K | 277 ± 2.8 | 3 | T447G | 283 ± 6.9* | 6 |
| T392S | 273 ± 7.1 | 7 | P448M | 254 ± 6.3 | 4 |
| S393F | 123 ± 1.5* | 7 | Y449N | 246 ± 10.0 | 5 |
| L394S | 252 ± 4.9 | 6 | A466S# | 184 ± 4.3* | 6 |
| Q395D | 314 ± 9.4* | 6 | K467S# | 164 ± 2.2* | 1 |
| P396C | 215 ± 8.8* | 5 | V468R | 324 ± 8.6* | 6 |
| V397E | 301 ± 11.1* | 8 | V469I | 322 ± 4.3* | 4 |
| V398P | 257 ± 3.4 | 7 | K470G# | 97 ± 1.3* | 7 |
| S400D | 194 ± 4.9* | 12 | S472T# | 96 ± 1.6* | 7 |
| R401N# | 147 ± 3.2* | 9 | R486K | 275 ± 4.9* | 8 |
| T404S | 233 ± 8.2 | 8 | R488N | 276 ± 5.3* | 6 |
| V405I | 255 ± 4.5 | 8 | G489N | 257 ± 3.1 | 5 |
| A406V | 262 ± 3.1 | 8 | Y499V | 265 ± 3.3 | 7 |
| R411A | 238 ± 6.6 | 6 | K501Q | 281 ± 3.6* | 8 |
| S418D | 253 ± 8.2 | 7 | K470D# | 89 ± 2.0* | 8 |
| P419I | 190 ± 3.5* | 10 | K470T# | 102 ± 4.0* | 8 |
| G422L | 237 ± 4.2 | 8 | K470W# | 102 ± 1.3* | 6 |
| G424E# | 189 ± 2.8* | 5 | S472A# | 134 ± 2.8* | 7 |
| G425T | 240 ± 2.5 | 8 | S472R# | 90 ± 3.1* | 7 |
| V427I# | 294 ± 5.2* | 6 | S472E# | 98 ± 2.2* | 6 |
↵* P < 0.05 by ANOVA, Bonferroni post hoc; #Residues that form part of the proposed PYD-106 binding pocket and have a significant effect on PYD-106 modulation.