Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T82665 | Target Info | |||
| Target Name | Protein arginine methyltransferase 5 (PRMT5) | ||||
| Synonyms | Shk1 kinase-binding protein 1 homolog; SKB1Hs; SKB1 homolog; SKB1; Protein arginine N-methyltransferase 5; Jak-binding protein 1; JBP1; IBP72; Histone-arginine N-methyltransferase PRMT5; HRMT1L5; 72 kDa ICln-binding protein | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PRMT5 | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Sinefungin | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)CC(CCC(C(=O)O)N)N)O)O)N | ||||
| InChI | 1S/C15H23N7O5/c16-6(1-2-7(17)15(25)26)3-8-10(23)11(24)14(27-8)22-5-21-9-12(18)19-4-20-13(9)22/h4-8,10-11,14,23-24H,1-3,16-17H2,(H,25,26)(H2,18,19,20)/t6-,7-,8+,10+,11+,14+/m0/s1 | ||||
| InChIKey | LMXOHSDXUQEUSF-YECHIGJVSA-N | ||||
| PubChem Compound ID | 65482 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6V0P PRMT5 complex bound to covalent PBM inhibitor BRD6711 | ||||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | No | [1] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHE 276 FCSYLQYLEY286 LSQNRPPPNA296 YELFAKGYED306 YLQSPLQPLM316 DNLESQTYEV 326 FEKDPIKYSQ336 YQQAIYKCLL346 DRVPEEEKDT356 NVQVLMVLGA366 GRGPLVNASL 376 RAAKQADRRI386 KLYAVEKNPN396 AVVTLENWQF406 EEWGSQVTVV416 SSDMREWVAP 426 EKADIIVSEL436 LGSFADNELS446 PECLDGAQHF456 LKDDGVSIPG466 EYTSFLAPIS 476 SSKLYNEVRA486 CREKDRDPEA496 QFEMPYVVRL506 HNFHQLSAPQ516 PCFTFSHPNR 526 DPMIDNNRYC536 TLEFPVEVNT546 VLHGFAGYFE556 TVLYQDITLS566 IRPETHSPGM 576 FSWFPILFPI586 KQPITVREGQ596 TICVRFWRCS606 NSKKVWYEWA616 VTAPVCSAIH 626 NPTGRSYTIG636 L
|
|||||
|
|
PRO314
3.278
LEU315
2.549
ASN318
4.729
LEU319
3.982
TYR324
1.963
PHE327
3.039
GLU328
3.668
LYS333
3.172
TYR334
2.679
LEU364
4.800
GLY365
2.481
ALA366
3.799
GLY367
2.681
ARG368
4.443
|
|||||
| PDB ID: 6V0N PRMT5 bound to PBM peptide from Riok1 | ||||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [2] |
| PDB Sequence |
VSSGRDLNCV
23 PEIADTLGAV33 AKQGFDFLCM43 PVFHPRFKRE53 FIQEPAKNRP63 GPQTRSDLLL 73 SGRDWNTLIV83 GKLSPWIRPD93 SKVEKIRRNS103 EAAMLQELNF113 GAYLGLPAFL 123 LPLNQEDNTN133 LARVLTNHIH143 TGHHSSMFWM153 RVPLVAPEDL163 RDDIIENAPT 173 THTEEYSGEE183 KTWMWWHNFR193 TLCDYSKRIA203 VALEIGADLP213 SNHVIDRWLG 223 EPIKAAILPT233 SIFLTNKKGF243 PVLSKMHQRL253 IFRLLKLEVQ263 FIITGTNHHS 273 EKEFCSYLQY283 LEYLSQNRPP293 PNAYELFAKG303 YEDYLQSPLQ313 PLMDNLESQT 323 YEVFEKDPIK333 YSQYQQAIYK343 CLLDRVPEEE353 KDTNVQVLMV363 LGAGRGPLVN 373 ASLRAAKQAD383 RRIKLYAVEK393 NPNAVVTLEN403 WQFEEWGSQV413 TVVSSDMREW 423 VAPEKADIIV433 SELLGSFADN443 ELSPECLDGA453 QHFLKDDGVS463 IPGEYTSFLA 473 PISSSKLYNE483 VRACREKDRD493 PEAQFEMPYV503 VRLHNFHQLS513 APQPCFTFSH 523 PNRDPMIDNN533 RYCTLEFPVE543 VNTVLHGFAG553 YFETVLYQDI563 TLSIRPETHS 573 PGMFSWFPIL583 FPIKQPITVR593 EGQTICVRFW603 RCSNSKKVWY613 EWAVTAPVCS 623 AIHNPTGRSY633 TIGL
|
|||||
|
|
PRO314
3.499
LEU315
3.509
LEU319
4.113
TYR324
2.676
PHE327
3.366
GLU328
4.719
LYS333
3.631
TYR334
2.695
LEU364
4.921
GLY365
2.876
ALA366
3.904
GLY367
3.517
PRO370
3.384
|
|||||
| PDB ID: 6V0O PRMT5 bound to the PBM peptide from pICln | ||||||
| Method | X-ray diffraction | Resolution | 2.86 Å | Mutation | No | [2] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
|
PRO314
2.958
LEU315
2.945
ASP317
4.417
ASN318
4.810
LEU319
3.287
TYR324
1.904
PHE327
3.226
GLU328
3.864
LYS333
2.916
TYR334
2.328
LEU364
4.840
GLY365
2.596
ALA366
3.169
GLY367
3.332
ARG368
4.432
GLY369
4.837
|
|||||
| PDB ID: 5EMJ Crystal structure of PRMT5:MEP50 with Compound 8 and sinefungin | ||||||
| Method | X-ray diffraction | Resolution | 2.27 Å | Mutation | No | [3] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SFG or .SFG2 or .SFG3 or :3SFG;style chemicals stick;color identity;select .A:314 or .A:315 or .A:319 or .A:324 or .A:328 or .A:333 or .A:334 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:370 or .A:371 or .A:391 or .A:392 or .A:393 or .A:394 or .A:418 or .A:419 or .A:420 or .A:421 or .A:435 or .A:436 or .A:444 or .A:449; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO314
4.456
LEU315
3.192
LEU319
4.043
TYR324
2.625
GLU328
4.354
LYS333
2.994
TYR334
2.800
LEU364
4.771
GLY365
3.038
ALA366
3.924
GLY367
3.686
ARG368
4.993
PRO370
3.273
|
|||||
| PDB ID: 4X60 Crystal structure of PRMT5:MEP50 with EPZ015666 and sinefungin | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [4] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SFG or .SFG2 or .SFG3 or :3SFG;style chemicals stick;color identity;select .A:314 or .A:315 or .A:319 or .A:324 or .A:328 or .A:333 or .A:334 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:370 or .A:371 or .A:391 or .A:392 or .A:393 or .A:394 or .A:418 or .A:419 or .A:420 or .A:421 or .A:435 or .A:436 or .A:444 or .A:449; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO314
4.543
LEU315
3.648
LEU319
4.042
TYR324
2.501
GLU328
4.237
LYS333
3.039
TYR334
2.554
LEU364
4.654
GLY365
3.105
ALA366
3.758
GLY367
3.632
ARG368
4.948
PRO370
3.149
|
|||||
| PDB ID: 5C9Z Crystal structure of PRMT5:MEP50 with EPZ015866 and sinefungin | ||||||
| Method | X-ray diffraction | Resolution | 2.36 Å | Mutation | No | [5] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SFG or .SFG2 or .SFG3 or :3SFG;style chemicals stick;color identity;select .A:314 or .A:315 or .A:319 or .A:324 or .A:328 or .A:333 or .A:334 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:370 or .A:371 or .A:391 or .A:392 or .A:393 or .A:394 or .A:418 or .A:419 or .A:420 or .A:421 or .A:435 or .A:436 or .A:444 or .A:449; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO314
4.533
LEU315
3.377
LEU319
3.988
TYR324
2.628
GLU328
4.237
LYS333
2.981
TYR334
2.611
LEU364
4.694
GLY365
3.011
ALA366
3.649
GLY367
3.633
ARG368
4.924
PRO370
3.240
|
|||||
| PDB ID: 5EMM Crystal structure of PRMT5:MEP50 with Compound 15 and sinefungin | ||||||
| Method | X-ray diffraction | Resolution | 2.37 Å | Mutation | No | [3] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SFG or .SFG2 or .SFG3 or :3SFG;style chemicals stick;color identity;select .A:314 or .A:315 or .A:319 or .A:324 or .A:328 or .A:333 or .A:334 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:370 or .A:371 or .A:391 or .A:392 or .A:393 or .A:394 or .A:418 or .A:419 or .A:420 or .A:421 or .A:435 or .A:436 or .A:449; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO314
4.587
LEU315
3.525
LEU319
4.125
TYR324
2.565
GLU328
3.950
LYS333
2.924
TYR334
2.458
LEU364
4.459
GLY365
3.025
ALA366
3.657
GLY367
3.765
ARG368
4.927
PRO370
3.136
|
|||||
| PDB ID: 5EMK Crystal structure of PRMT5:MEP50 with Compound 9 and sinefungin | ||||||
| Method | X-ray diffraction | Resolution | 2.52 Å | Mutation | No | [3] |
| PDB Sequence |
RVSSGRDLNC
22 VPEIADTLGA32 VAKQGFDFLC42 MPVFHPRFKR52 EFIQEPAKNR62 PGPQTRSDLL 72 LSGRDWNTLI82 VGKLSPWIRP92 DSKVEKIRRN102 SEAAMLQELN112 FGAYLGLPAF 122 LLPLNQEDNT132 NLARVLTNHI142 HTGHHSSMFW152 MRVPLVAPED162 LRDDIIENAP 172 TTHTEEYSGE182 EKTWMWWHNF192 RTLCDYSKRI202 AVALEIGADL212 PSNHVIDRWL 222 GEPIKAAILP232 TSIFLTNKKG242 FPVLSKMHQR252 LIFRLLKLEV262 QFIITGTNHH 272 SEKEFCSYLQ282 YLEYLSQNRP292 PPNAYELFAK302 GYEDYLQSPL312 QPLMDNLESQ 322 TYEVFEKDPI332 KYSQYQQAIY342 KCLLDRVPEE352 EKDTNVQVLM362 VLGAGRGPLV 372 NASLRAAKQA382 DRRIKLYAVE392 KNPNAVVTLE402 NWQFEEWGSQ412 VTVVSSDMRE 422 WVAPEKADII432 VSELLGSFAD442 NELSPECLDG452 AQHFLKDDGV462 SIPGEYTSFL 472 APISSSKLYN482 EVRACREKDR492 DPEAQFEMPY502 VVRLHNFHQL512 SAPQPCFTFS 522 HPNRDPMIDN532 NRYCTLEFPV542 EVNTVLHGFA552 GYFETVLYQD562 ITLSIRPETH 572 SPGMFSWFPI582 LFPIKQPITV592 REGQTICVRF602 WRCSNSKKVW612 YEWAVTAPVC 622 SAIHNPTGRS632 YTIGL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SFG or .SFG2 or .SFG3 or :3SFG;style chemicals stick;color identity;select .A:314 or .A:315 or .A:319 or .A:324 or .A:328 or .A:333 or .A:334 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:370 or .A:371 or .A:391 or .A:392 or .A:393 or .A:394 or .A:418 or .A:419 or .A:420 or .A:421 or .A:435 or .A:436 or .A:444 or .A:449; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO314
4.010
LEU315
3.702
LEU319
4.318
TYR324
2.395
GLU328
4.124
LYS333
2.829
TYR334
2.638
LEU364
4.599
GLY365
3.124
ALA366
3.219
GLY367
3.651
ARG368
4.930
PRO370
3.291
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of a First-in-Class Inhibitor of the PRMT5-Substrate Adaptor Interaction. J Med Chem. 2021 Aug 12;64(15):11148-11168. | ||||
| REF 2 | Molecular basis for substrate recruitment to the PRMT5 methylosome. Mol Cell. 2021 Sep 2;81(17):3481-3495.e7. | ||||
| REF 3 | Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666. ACS Med Chem Lett. 2015 Dec 2;7(2):162-6. | ||||
| REF 4 | A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015 Jun;11(6):432-7. | ||||
| REF 5 | Crystal structure of PRMT5/MEP50 complex with sinefungin and 15866 | ||||
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