Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T28309 | Target Info | |||
| Target Name | Mucolipin-1 (TRPML1) | ||||
| Synonyms | Transient receptor potential channel mucolipin 1; TRPML1; Mucolipidin; MSTP080; ML4; ML1; MG-2 | ||||
| Target Type | Preclinical Target | ||||
| Gene Name | MCOLN1 | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine | Ligand Info | |||||
| Structure Description | Structure of human TRPML1 with ML-SI3 | PDB:7MGL | ||||
| Method | Electron microscopy | Resolution | 2.90 Å | Mutation | No | [1] |
| PDB Sequence |
DLRRRLKYFF
49 MSPCDKFRAK59 GRKPCKLMLQ69 VVKILVVTVQ79 LILFGLSNQL89 AVTFREENTI 99 AFRHLFLLGY109 SDGADDTFAA119 YTREQLYQAI129 FHAVDQYLAL139 PDVSLGRYAY 149 VRGGGDPWTN159 GSGLALCQRY169 YHRGHVDPAN179 DTFDIDPMVV189 TDCIQVDPPE 199 RSSYKNLTLK224 FHKLVNVTIH234 FRLKTINLQS244 LINNEIPDCY254 TFSVLITFDN 264 KAHSGRIPIS274 LETQAHIQEC284 KHPSVFQHGD294 NSFRLLFDVV304 VILTCSLSFL 314 LCARSLLRGF324 LLQNEFVGFM334 WRQRGRVISL344 WERLEFVNGW354 YILLVTSDVL 364 TISGTIMKIG374 IEAKNLASYD384 VCSILLGTST394 LLVWVGVIRY404 LTFFHNYNIL 414 IATLRVALPS424 VMRFCCCVAV434 IYLGYCFCGW444 IVLGPYHVKF454 RSLSMVSECL 464 FSLINGDDMF474 VTFAAMQAQQ484 GRSSLVWLFS494 QLYLYSFISL504 FIYMVLSLFI 514 ALITGAYDTI524 KH
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| Ligand Name: N-{(1S,2S)-2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl}benzenesulfonamide | Ligand Info | |||||
| Structure Description | Structure of human TRPML1 with ML-SI3 | PDB:7MGL | ||||
| Method | Electron microscopy | Resolution | 2.90 Å | Mutation | No | [1] |
| PDB Sequence |
DLRRRLKYFF
49 MSPCDKFRAK59 GRKPCKLMLQ69 VVKILVVTVQ79 LILFGLSNQL89 AVTFREENTI 99 AFRHLFLLGY109 SDGADDTFAA119 YTREQLYQAI129 FHAVDQYLAL139 PDVSLGRYAY 149 VRGGGDPWTN159 GSGLALCQRY169 YHRGHVDPAN179 DTFDIDPMVV189 TDCIQVDPPE 199 RSSYKNLTLK224 FHKLVNVTIH234 FRLKTINLQS244 LINNEIPDCY254 TFSVLITFDN 264 KAHSGRIPIS274 LETQAHIQEC284 KHPSVFQHGD294 NSFRLLFDVV304 VILTCSLSFL 314 LCARSLLRGF324 LLQNEFVGFM334 WRQRGRVISL344 WERLEFVNGW354 YILLVTSDVL 364 TISGTIMKIG374 IEAKNLASYD384 VCSILLGTST394 LLVWVGVIRY404 LTFFHNYNIL 414 IATLRVALPS424 VMRFCCCVAV434 IYLGYCFCGW444 IVLGPYHVKF454 RSLSMVSECL 464 FSLINGDDMF474 VTFAAMQAQQ484 GRSSLVWLFS494 QLYLYSFISL504 FIYMVLSLFI 514 ALITGAYDTI524 KH
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| Ligand Name: 2-{2-oxo-2-[(4S)-2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl]ethyl}-1H-isoindole-1,3(2H)-dione | Ligand Info | |||||
| Structure Description | Human TRPML1 channel structure in agonist-bound open conformation | PDB:5WJ9 | ||||
| Method | Electron microscopy | Resolution | 3.49 Å | Mutation | No | [2] |
| PDB Sequence |
EEDLRRRLKY
47 FFMSPCDKFR57 AKGRKPCKLM67 LQVVKILVVT77 VQLILFGLSN87 QLAVTFREEN 97 TIAFRHLFLL107 GYSDGADDTF117 AAYTREQLYQ127 AIFHAVDQYL137 ALPDVSLGRY 147 AYVRGGGDPW157 TNGSGLALCQ167 RYYHRGHVDP177 ANDTFDIDPM187 VVTDCIQVDP 197 PERPPPPPSS217 YKNLTLKFHK227 LVNVTIHFRL237 KTINLQSLIN247 NEIPDCYTFS 257 VLITFDNKAH267 SGRIPISLET277 QAHIQECKHP287 SVFQHGDNSF297 RLLFDVVVIL 307 TCSLSFLLCA317 RSLLRGFLLQ327 NEFVGFMWRQ337 RGRVISLWER347 LEFVNGWYIL 357 LVTSDVLTIS367 GTIMKIGIEA377 KNLASYDVCS387 ILLGTSTLLV397 WVGVIRYLTF 407 FHNYNILIAT417 LRVALPSVMR427 FCCCVAVIYL437 GYCFCGWIVL447 GPYHVKFRSL 457 SMVSECLFSL467 INGDDMFVTF477 AAMQAQQGRS487 SLVWLFSQLY497 LYSFISLFIY 507 MVLSLFIALI517 TGAYDTIKH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AQV or .AQV2 or .AQV3 or :3AQV;style chemicals stick;color identity;select .A:429 or .A:432 or .A:433 or .A:436 or .A:461 or .A:465 or .A:468 or .A:505 or .A:513; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: [(2r)-2-Octanoyloxy-3-[oxidanyl-[(1r,2r,3s,4r,5r,6s)-2,3,6-Tris(Oxidanyl)-4,5-Diphosphonooxy-Cyclohexyl]oxy-Phosphoryl]oxy-Propyl] Octanoate | Ligand Info | |||||
| Structure Description | cryo-EM structure of human TRPML1 with PI45P2 | PDB:6E7Y | ||||
| Method | Electron microscopy | Resolution | 3.57 Å | Mutation | No | [3] |
| PDB Sequence |
EEDLRRRLKY
47 FFMSPCDKFR57 AKGRKPCKLM67 LQVVKILVVT77 VQLILFGLSN87 QLAVTFREEN 97 TIAFRHLFLL107 GYSDGADDTF117 AAYTREQLYQ127 AIFHAVDQYL137 ALPDVSLGRY 147 AYVRGGGDPW157 TNGSGLALCQ167 RYYHRGHVDP177 ANDTFDIDPM187 VVTDCIQVDP 197 PERPSSYKNL221 TLKFHKLVNV231 TIHFRLKTIN241 LQSLINNEIP251 DCYTFSVLIT 261 FDNKAHSGRI271 PISLETQAHI281 QECKHPSVFQ291 HGDNSFRLLF301 DVVVILTCSL 311 SFLLCARSLL321 RGFLLQNEFV331 GFMWRQRGRV341 ISLWERLEFV351 NGWYILLVTS 361 DVLTISGTIM371 KIGIEAKNLA381 SYDVCSILLG391 TSTLLVWVGV401 IRYLTFFHNY 411 NILIATLRVA421 LPSVMRFCCC431 VAVIYLGYCF441 CGWIVLGPYH451 VKFRSLSMVS 461 ECLFSLINGD471 DMFVTFAAMQ481 AQQGRSSLVW491 LFSQLYLYSF501 ISLFIYMVLS 511 LFIALITGAY521 DTIKH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PIO or .PIO2 or .PIO3 or :3PIO;style chemicals stick;color identity;select .A:47 or .A:50 or .A:55 or .A:59 or .A:61 or .A:62 or .A:65 or .A:319 or .A:322 or .A:355; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (1R,2S,3S,4R,5S,6R)-5-{[(R)-[(2R)-2,3-bis{[(1S)-1-hydroxyoctyl]oxy}propoxy](hydroxy)phosphoryl]oxy}-2,4,6-trihydroxycyclohexane-1,3-diyl bis[dihydrogen (phosphate)] | Ligand Info | |||||
| Structure Description | cryo-EM structure of human TRPML1 with PI35P2 | PDB:6E7P | ||||
| Method | Electron microscopy | Resolution | 3.50 Å | Mutation | No | [3] |
| PDB Sequence |
EEDLRRRLKY
47 FFMSPCDKFR57 AKGRKPCKLM67 LQVVKILVVT77 VQLILFGLSN87 QLAVTFREEN 97 TIAFRHLFLL107 GYSDGADDTF117 AAYTREQLYQ127 AIFHAVDQYL137 ALPDVSLGRY 147 AYVRGGGDPW157 TNGSGLALCQ167 RYYHRGHVDP177 ANDTFDIDPM187 VVTDCIQVDP 197 PERPSSYKNL221 TLKFHKLVNV231 TIHFRLKTIN241 LQSLINNEIP251 DCYTFSVLIT 261 FDNKAHSGRI271 PISLETQAHI281 QECKHPSVFQ291 HGDNSFRLLF301 DVVVILTCSL 311 SFLLCARSLL321 RGFLLQNEFV331 GFMWRQRGRV341 ISLWERLEFV351 NGWYILLVTS 361 DVLTISGTIM371 KIGIEAKNLA381 SYDVCSILLG391 TSTLLVWVGV401 IRYLTFFHNY 411 NILIATLRVA421 LPSVMRFCCC431 VAVIYLGYCF441 CGWIVLGPYH451 VKFRSLSMVS 461 ECLFSLINGD471 DMFVTFAAMQ481 AQQGRSSLVW491 LFSQLYLYSF501 ISLFIYMVLS 511 LFIALITGAY521 DTIKH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HZ7 or .HZ72 or .HZ73 or :3HZ7;style chemicals stick;color identity;select .A:47 or .A:55 or .A:59 or .A:61 or .A:65 or .A:315 or .A:318 or .A:319 or .A:322 or .A:355 or .A:403; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Atomic insights into ML-SI3 mediated human TRPML1 inhibition. Structure. 2021 Nov 4;29(11):1295-1302.e3. | ||||
| REF 2 | Human TRPML1 channel structures in open and closed conformations. Nature. 2017 Oct 19;550(7676):366-370. | ||||
| REF 3 | Structural basis for PtdInsP(2)-mediated human TRPML1 regulation. Nat Commun. 2018 Oct 10;9(1):4192. | ||||
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