Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T27812 | Target Info | |||
| Target Name | Serotonin transporter (SERT) | ||||
| Synonyms | Solute carrier family 6 member 4; HTT; 5HTT; 5HT transporter | ||||
| Target Type | Successful Target | ||||
| Gene Name | SLC6A4 | ||||
| Biochemical Class | Neurotransmitter:sodium symporter | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Paroxetine | Ligand Info | |||
| Canonical SMILES | C1CNCC(C1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4 | ||||
| InChI | 1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1 | ||||
| InChIKey | AHOUBRCZNHFOSL-YOEHRIQHSA-N | ||||
| PubChem Compound ID | 43815 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6VRH Cryo-EM structure of the wild-type human serotonin transporter complexed with paroxetine and 8B6 Fab | ||||||
| Method | Electron microscopy | Resolution | 3.30 Å | Mutation | No | [1] |
| PDB Sequence |
GERETWGKKV
86 DFLLSVIGYA96 VDLGNVWRFP106 YICYQNGGGA116 FLLPYTIMAI126 FGGIPLFYME 136 LALGQYHRNG146 CISIWRKICP156 IFKGIGYAIC166 IIAFYIASYY176 NTIMAWALYY 186 LISSFTDQLP196 WTSCKNSWNT206 GNCTNYFSED216 NITWTLHSTS226 PAEEFYTRHV 236 LQIHRSKGLQ246 DLGGISWQLA256 LCIMLIFTVI266 YFSIWKGVKT276 SGKVVWVTAT 286 FPYIILSVLL296 VRGATLPGAW306 RGVLFYLKPN316 WQKLLETGVW326 IDAAAQIFFS 336 LGPGFGVLLA346 FASYNKFNNN356 CYQDALVTSV366 VNCMTSFVSG376 FVIFTVLGYM 386 AEMRNEDVSE396 VAKDAGPSLL406 FITYAEAIAN416 MPASTFFAII426 FFLMLITLGL 436 DSTFAGLEGV446 ITAVLDEFPH456 VWAKRRERFV466 LAVVITCFFG476 SLVTLTFGGA 486 YVVKLLEEYA496 TGPAVLTVAL506 IEAVAVSWFY516 GITQFCRDVK526 EMLGFSPGWF 536 WRICWVAISP546 LFLLFIICSF556 LMSPPQLRLF566 QYNYPYWSII576 LGYCIGTSSF 586 ICIPTYIAYR596 LIITPGTFKE606 RIIKSITPET616 P
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TYR95
2.894
ALA96
3.518
VAL97
4.798
ASP98
3.347
ILE168
4.771
ALA169
3.343
ILE172
3.460
ALA173
3.568
TYR176
4.022
PHE335
3.434
SER336
3.583
|
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| PDB ID: 5I6X X-ray structure of the ts3 human serotonin transporter complexed with paroxetine at the central site | ||||||
| Method | X-ray diffraction | Resolution | 3.14 Å | Mutation | Yes | [2] |
| PDB Sequence |
GSQGERETWG
83 KKVDFLLSVI93 GYAVDLGNVW103 RFPYICAQNG113 GGAFLLPYTI123 MAIFGGIPLF 133 YMELALGQYH143 RNGCISIWRK153 ICPIFKGIGY163 AICIIAFYIA173 SYYNTIMAWA 183 LYYLISSFTD193 QLPWTSCKNS203 WNTGNCTNYF213 SEDNITWTLH223 STSPAEEFYT 233 RHVLQIHRSK243 GLQDLGGISW253 QLALCIMLIF263 TVIYFSIWKG273 VKTSGKVVWV 283 TATFPYIALS293 VLLVRGATLP303 GAWRGVLFYL313 KPNWQKLLET323 GVWIDAAAQI 333 FFSLGPGFGV343 LLAFASYNKF353 NNNCYQDALV363 TSVVNCMTSF373 VSGFVIFTVL 383 GYMAEMRNED393 VSEVAKDAGP403 SLLFITYAEA413 IANMPASTFF423 AIIFFLMLIT 433 LGLDSSFAGL443 EGVITAVLDE453 FPHVWAKRRE463 RFVLAVVITC473 FFGSLVTLTF 483 GGAYVVKLLE493 EYATGPAVLT503 VALIEAVAVS513 WFYGITQFCR523 DVKEMLGFSP 533 GWFWRICWVA543 ISPLFLLFII553 ASFLMSPPQL563 RLFQYNYPYW573 SIILGYAIGT 583 SSFICIPTYI593 AYRLIITPGT603 FKERIIKSIT613 PETP
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TYR95
3.187
ALA96
3.157
VAL97
4.680
ASP98
3.088
ASN101
4.996
ILE168
4.867
ALA169
3.444
ILE172
3.234
ALA173
4.020
TYR176
3.733
PHE335
3.239
|
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| PDB ID: 6AWN X-ray structure of the S439T human serotonin transporter complexed with paroxetine at the central site | ||||||
| Method | X-ray diffraction | Resolution | 3.62 Å | Mutation | Yes | [3] |
| PDB Sequence |
GSQGERETWG
83 KKVDFLLSVI93 GYAVDLGNVW103 RFPYICAQNG113 GGAFLLPYTI123 MAIFGGIPLF 133 YMELALGQYH143 RNGCISIWRK153 ICPIFKGIGY163 AICIIAFYIA173 SYYNTIMAWA 183 LYYLISSFTD193 QLPWTSCKNS203 WNTGNCTNYF213 SEDNITWTLH223 STSPAEEFYT 233 RHVLQIHRSK243 GLQDLGGISW253 QLALCIMLIF263 TVIYFSIWKG273 VKTSGKVVWV 283 TATFPYIALS293 VLLVRGATLP303 GAWRGVLFYL313 KPNWQKLLET323 GVWIDAAAQI 333 FFSLGPGFGV343 LLAFASYNKF353 NNNCYQDALV363 TSVVNCMTSF373 VSGFVIFTVL 383 GYMAEMRNED393 VSEVAKDAGP403 SLLFITYAEA413 IANMPASTFF423 AIIFFLMLIT 433 LGLDSTFAGL443 EGVITAVLDE453 FPHVWAKRRE463 RFVLAVVITC473 FFGSLVTLTF 483 GGAYVVKLLE493 EYATGPAVLT503 VALIEAVAVS513 WFYGITQFCR523 DVKEMLGFSP 533 GWFWRICWVA543 ISPLFLLFII553 ASFLMSPPQL563 RLFQYNYPYW573 SIILGYAIGT 583 SSFICIPTYI593 AYRLIITPGT603 FKERIIKSIT613 PETP
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| PDB ID: 6DZW Cryo-EM structure of the ts2-inactive human serotonin transporter in complex with paroxetine and 15B8 Fab and 8B6 ScFv | ||||||
| Method | Electron microscopy | Resolution | 4.30 Å | Mutation | No | [4] |
| PDB Sequence |
RETWGKKVDF
88 LLSVIGYAVD98 LGNVWRFPYI108 CAQNGGGAFL118 LPYTIMAIFG128 GIPLFYMELA 138 LGQYHRNGCI148 SIWRKICPIF158 KGIGYAICII168 AFYIASYYNT178 IMAWALYYLI 188 SSFTDQLPWT198 SCKNSWNTGN208 CTNYFSEDNI218 TWTLHSTSPA228 EEFYTRHVLQ 238 IHRSKGLQDL248 GGISWQLALC258 IMLIFTVIYF268 SIWKGVKTSG278 KVVWVTATFP 288 YIALSVLLVR298 GATLPGAWRG308 VLFYLKPNWQ318 KLLETGVWID328 AAAQIFFSLG 338 PGFGVLLAFA348 SYNKFNNNCY358 QDALVTSVVN368 CMTSFVSGFV378 IFTVLGYMAE 388 MRNEDVSEVA398 KDAGPSLLFI408 TYAEAIANMP418 ASTFFAIIFF428 LMLITLGLDS 438 TFAGLEGVIT448 AVLDEFPHVW458 AKRRERFVLA468 VVITCFFGSL478 VTLTFGGAYV 488 VKLLEEYATG498 PAVLTVALIE508 AVAVSWFYGI518 TQFCRDVKEM528 LGFSPGWFWR 538 ICWVAISPLF548 LLFIIASFLM558 SPPQLRLFQY568 NYPYWSIILG578 YAIGTSSFIC 588 IPTYIAYRLI598 ITPGTFKERI608 IKSITPE
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Click to Show 3D Structure of This Binding Site
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Chemical and structural investigation of the paroxetine-human serotonin transporter complex. Elife. 2020 Jul 3;9:e56427. | ||||
| REF 2 | X-ray structures and mechanism of the human serotonin transporter. Nature. 2016 Apr 21;532(7599):334-9. | ||||
| REF 3 | Structural basis for recognition of diverse antidepressants by the human serotonin transporter. Nat Struct Mol Biol. 2018 Feb;25(2):170-175. | ||||
| REF 4 | Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport. Nature. 2019 May;569(7754):141-145. | ||||
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