Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T97621 | Target Info | |||
| Target Name | cAMP-dependent chloride channel F508 deletion (CFTR del F508) | ||||
| Synonyms | cAMP-dependent chloride channel (del F508); Cystic fibrosis transmembrane conductance regulator (del F508); Channel conductance-controlling ATPase; CFTR; ATP-binding cassette sub-family C member 7 (del F508); ABCC7 (del F508) | ||||
| Target Type | Successful Target | ||||
| Gene Name | CFTR | ||||
| Biochemical Class | ABC transporter | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Elexacaftor | Ligand Info | |||
| Canonical SMILES | CC1CC(N(C1)C2=C(C=CC(=N2)N3C=CC(=N3)OCC(C)(C)C(F)(F)F)C(=O)NS(=O)(=O)C4=CN(N=C4C)C)(C)C | ||||
| InChI | 1S/C26H34F3N7O4S/c1-16-12-25(5,6)35(13-16)22-18(23(37)33-41(38,39)19-14-34(7)31-17(19)2)8-9-20(30-22)36-11-10-21(32-36)40-15-24(3,4)26(27,28)29/h8-11,14,16H,12-13,15H2,1-7H3,(H,33,37)/t16-/m0/s1 | ||||
| InChIKey | MVRHVFSOIWFBTE-INIZCTEOSA-N | ||||
| PubChem Compound ID | 134587348 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 8EIO The complex of phosphorylated human delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) with elexacaftor (VX-445), lumacaftor (VX-809) and ATP/Mg | ||||||
| Method | Electron microscopy | Resolution | 2.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
MQRSPLEKAS
10 VVSKLFFSWT20 RPILRKGYRQ30 RLELSDIYQI40 PSVDSADNLS50 EKLEREWDRE 60 LASKKNPKLI70 NALRRCFFWR80 FMFYGIFLYL90 GEVTKAVQPL100 LLGRIIASYD 110 PDNKEERSIA120 IYLGIGLCLL130 FIVRTLLLHP140 AIFGLHHIGM150 QMRIAMFSLI 160 YKKTLKLSSR170 VLDKISIGQL180 VSLLSNNLNK190 FDEGLALAHF200 VWIAPLQVAL 210 LMGLIWELLQ220 ASAFCGLGFL230 IVLALFQAGL240 GRMMMKYRDQ250 RAGKISERLV 260 ITSEMIENIQ270 SVKAYCWEEA280 MEKMIENLRQ290 TELKLTRKAA300 YVRYFNSSAF 310 FFSGFFVVFL320 SVLPYALIKG330 IILRKIFTTI340 SFCIVLRMAV350 TRQFPWAVQT 360 WYDSLGAINK370 IQDFLQKQEY380 KTLEYNLTTT390 EVVMENVTAF400 WEGTPVLKDI 444 NFKIERGQLL454 AVAGSTGAGK464 TSLLMVIMGE474 LEPSEGKIKH484 SGRISFCSQF 494 SWIMPGTIKE504 NIIGVSYDEY515 RYRSVIKACQ525 LEEDISKFAE535 KDNIVLGEGG 545 ITLSGGQRAR555 ISLARAVYKD565 ADLYLLDSPF575 GYLDVLTEKE585 IFESCVCKLM 595 ANKTRILVTS605 KMEHLKKADK615 ILILHEGSSY625 FYGTFSELQN635 LWNTYLRYIT 854 VHKSLIFVLI864 WCLVIFLAEV874 AASLVVLWLL884 GSYAVIITST910 SSYYVFYIYV 920 GVADTLLAMG930 FFRGLPLVHT940 LITVSKILHH950 KMLHSVLQAP960 MSTLNTLKAG 970 GILNRFSKDI980 AILDDLLPLT990 IFDFIQLLLI1000 VIGAIAVVAV1010 LQPYIFVATV 1020 PVIVAFIMLR1030 AYFLQTSQQL1040 KQLESEGRSP1050 IFTHLVTSLK1060 GLWTLRAFGR 1070 QPYFETLFHK1080 ALNLHTANWF1090 LYLSTLRWFQ1100 MRIEMIFVIF1110 FIAVTFISIL 1120 TTGEGEGRVG1130 IILTLAMNIM1140 STLQWAVNSS1150 IDVDSLMRSV1160 SRVFKFIDMP 1170 TEGIWPSGGQ1209 MTVKDLTAKY1219 TEGGNAILEN1229 ISFSISPGQR1239 VGLLGRTGSG 1249 KSTLLSAFLR1259 LLNTEGEIQI1269 DGVSWDSITL1279 QQWRKAFGVI1289 PQKVFIFSGT 1299 FRKNLDPYEQ1309 WSDQEIWKVA1319 DEVGLRSVIE1329 QFPGKLDFVL1339 VDGGCVLSHG 1349 HKQLMCLARS1359 VLSKAKILLL1369 DQPSAHLDPV1379 TYQIIRRTLK1389 QAFADCTVIL 1399 CEHRIEAMLE1409 CQQFLVIEEN1419 KVRQYDSIQK1429 LLNERSLFRQ1439 AISPSDRVKL 1449 FP
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| PDB ID: 8EIQ The complex of phosphorylated human delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) with Trikafta [elexacaftor (VX-445), tezacaftor (VX-661), ivacaftor (VX-770)] and ATP/Mg | ||||||
| Method | Electron microscopy | Resolution | 3.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
MQRSPLEKAS
10 VVSKLFFSWT20 RPILRKGYRQ30 RLELSDIYQI40 PSVDSADNLS50 EKLEREWDRE 60 LASKKNPKLI70 NALRRCFFWR80 FMFYGIFLYL90 GEVTKAVQPL100 LLGRIIASYD 110 PDNKEERSIA120 IYLGIGLCLL130 FIVRTLLLHP140 AIFGLHHIGM150 QMRIAMFSLI 160 YKKTLKLSSR170 VLDKISIGQL180 VSLLSNNLNK190 FDEGLALAHF200 VWIAPLQVAL 210 LMGLIWELLQ220 ASAFCGLGFL230 IVLALFQAGL240 GRMMMKYRDQ250 RAGKISERLV 260 ITSEMIENIQ270 SVKAYCWEEA280 MEKMIENLRQ290 TELKLTRKAA300 YVRYFNSSAF 310 FFSGFFVVFL320 SVLPYALIKG330 IILRKIFTTI340 SFCIVLRMAV350 TRQFPWAVQT 360 WYDSLGAINK370 IQDFLQKQEY380 KTLEYNLTTT390 EVVMENVTAF400 WEGTPVLKDI 444 NFKIERGQLL454 AVAGSTGAGK464 TSLLMVIMGE474 LEPSEGKIKH484 SGRISFCSQF 494 SWIMPGTIKE504 NIIGVSYDEY515 RYRSVIKACQ525 LEEDISKFAE535 KDNIVLGEGG 545 ITLSGGQRAR555 ISLARAVYKD565 ADLYLLDSPF575 GYLDVLTEKE585 IFESCVCKLM 595 ANKTRILVTS605 KMEHLKKADK615 ILILHEGSSY625 FYGTFSELQN635 LWNTYLRYIT 854 VHKSLIFVLI864 WCLVIFLAEV874 AASLVVLWLL884 GSYAVIITST910 SSYYVFYIYV 920 GVADTLLAMG930 FFRGLPLVHT940 LITVSKILHH950 KMLHSVLQAP960 MSTLNTLKAG 970 GILNRFSKDI980 AILDDLLPLT990 IFDFIQLLLI1000 VIGAIAVVAV1010 LQPYIFVATV 1020 PVIVAFIMLR1030 AYFLQTSQQL1040 KQLESEGRSP1050 IFTHLVTSLK1060 GLWTLRAFGR 1070 QPYFETLFHK1080 ALNLHTANWF1090 LYLSTLRWFQ1100 MRIEMIFVIF1110 FIAVTFISIL 1120 TTGEGEGRVG1130 IILTLAMNIM1140 STLQWAVNSS1150 IDVDSLMRSV1160 SRVFKFIDMP 1170 TEGIWPSGGQ1209 MTVKDLTAKY1219 TEGGNAILEN1229 ISFSISPGQR1239 VGLLGRTGSG 1249 KSTLLSAFLR1259 LLNTEGEIQI1269 DGVSWDSITL1279 QQWRKAFGVI1289 PQKVFIFSGT 1299 FRKNLDPYEQ1309 WSDQEIWKVA1319 DEVGLRSVIE1329 QFPGKLDFVL1339 VDGGCVLSHG 1349 HKQLMCLARS1359 VLSKAKILLL1369 DQPSAHLDPV1379 TYQIIRRTLK1389 QAFADCTVIL 1399 CEHRIEAMLE1409 CQQFLVIEEN1419 KVRQYDSIQK1429 LLNERSLFRQ1439 AISPSDRVKL 1449 FP
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| PDB ID: 8EIG The complex of phosphorylated human delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) with elexacaftor (VX-445) and ATP/Mg | ||||||
| Method | Electron microscopy | Resolution | 3.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
RSPLEKASVV
12 SKLFFSWTRP22 ILRKGYRQRL32 ELSDIYQIPS42 VDSADNLSEK52 LEREWDRELA 62 SKKNPKLINA72 LRRCFFWRFM82 FYGIFLYLGE92 VTKAVQPLLL102 GRIIASYDPD 112 NKEERSIAIY122 LGIGLCLLFI132 VRTLLLHPAI142 FGLHHIGMQM152 RIAMFSLIYK 162 KTLKLSSRVL172 DKISIGQLVS182 LLSNNLNKFD192 EGLALAHFVW202 IAPLQVALLM 212 GLIWELLQAS222 AFCGLGFLIV232 LALFQAGLGR242 MMMKYRDQRA252 GKISERLVIT 262 SEMIENIQSV272 KAYCWEEAME282 KMIENLRQTE292 LKLTRKAAYV302 RYFNSSAFFF 312 SGFFVVFLSV322 LPYALIKGII332 LRKIFTTISF342 CIVLRMAVTR352 QFPWAVQTWY 362 DSLGAINKIQ372 DFLQKQEYKT382 LEYNLTTTEV392 VMENVTAFWE402 GTPVLKDINF 446 KIERGQLLAV456 AGSTGAGKTS466 LLMVIMGELE476 PSEGKIKHSG486 RISFCSQFSW 496 IMPGTIKENI506 IGVSYDEYRY517 RSVIKACQLE527 EDISKFAEKD537 NIVLGEGGIT 547 LSGGQRARIS557 LARAVYKDAD567 LYLLDSPFGY577 LDVLTEKEIF587 ESCVCKLMAN 597 KTRILVTSKM607 EHLKKADKIL617 ILHEGSSYFY627 GTFSELQNLW846 NTYLRYITVH 856 KSLIFVLIWC866 LVIFLAEVAA876 SLVVLWLLGN886 TPSYAVIITS909 TSSYYVFYIY 919 VGVADTLLAM929 GFFRGLPLVH939 TLITVSKILH949 HKMLHSVLQA959 PMSTLNTLKA 969 GGILNRFSKD979 IAILDDLLPL989 TIFDFIQLLL999 IVIGAIAVVA1009 VLQPYIFVAT 1019 VPVIVAFIML1029 RAYFLQTSQQ1039 LKQLESEGRS1049 PIFTHLVTSL1059 KGLWTLRAFG 1069 RQPYFETLFH1079 KALNLHTANW1089 FLYLSTLRWF1099 QMRIEMIFVI1109 FFIAVTFISI 1119 LTTGEGEGRV1129 GIILTLAMNI1139 MSTLQWAVNS1149 SIDVDSLMRS1159 VSRVFKFIDM 1169 PTEGIWPSGG1208 QMTVKDLTAK1218 YTEGGNAILE1228 NISFSISPGQ1238 RVGLLGRTGS 1248 GKSTLLSAFL1258 RLLNTEGEIQ1268 IDGVSWDSIT1278 LQQWRKAFGV1288 IPQKVFIFSG 1298 TFRKNLDPYE1308 QWSDQEIWKV1318 ADEVGLRSVI1328 EQFPGKLDFV1338 LVDGGCVLSH 1348 GHKQLMCLAR1358 SVLSKAKILL1368 LDQPSAHLDP1378 VTYQIIRRTL1388 KQAFADCTVI 1398 LCEHRIEAML1408 ECQQFLVIEE1418 NKVRQYDSIQ1428 K
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| References | Top | ||||
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| REF 1 | Molecular structures reveal synergistic rescue of Delta508 CFTR by Trikafta modulators. Science. 2022 Oct 21;378(6617):284-290. | ||||
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