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 | (1S,2S,3S,5R)-3-{[6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl]oxy}-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol | Ligand Info | |||
| Canonical SMILES | CC1=C2C=CN(C2=NC=N1)C3CC(C(C3O)O)OC4=C5CNCCC5=C(C(=C4)C(F)F)F | ||||
| InChI | 1S/C22H23F3N4O3/c1-10-11-3-5-29(22(11)28-9-27-10)15-7-17(20(31)19(15)30)32-16-6-13(21(24)25)18(23)12-2-4-26-8-14(12)16/h3,5-6,9,15,17,19-21,26,30-31H,2,4,7-8H2,1H3/t15-,17+,19+,20-/m1/s1 | ||||
| InChIKey | HBGHQRGHFNTSDP-DJABAAGCSA-N | ||||
| PubChem Compound ID | 132200405 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7MX7 PRMT5:MEP50 complexed with inhibitor PF-06939999 | ||||||
| Method | X-ray diffraction | Resolution | 2.49 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 QFIITGTNHH 272 SCSYLQYLEY286 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
3.501
LEU315
3.611
LEU319
4.446
TYR324
2.520
PHE327
2.944
GLU328
4.309
LYS333
3.524
TYR334
3.355
GLY365
3.474
ALA366
3.783
GLY367
3.168
ARG368
3.865
PRO370
3.527
VAL391
4.587
|
|||||
| PDB ID: 7MXN PRMT5(M420T mutant):MEP50 complexed with inhibitor PF-06939999 | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | Yes | [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 QFIITGTNHH 272 SCSYLQYLEY286 LSQNRPPPNA296 YELFAKGYED306 YLQSPLQPLM316 DNLESQTYEV 326 FEKDPIKYSQ336 YQQAIYKCLL346 DRVPEEEKDT356 NVQVLMVLGA366 GRGPLVNASL 376 RAAKQADRRI386 KLYAVEKNPN396 AVVTLENWQF406 EEWGSQVTVV416 SSDTREWVAP 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
3.737
LEU315
3.517
LEU319
4.384
TYR324
2.529
PHE327
2.955
GLU328
4.318
LYS333
3.507
TYR334
3.333
LEU364
4.773
GLY365
3.478
ALA366
3.857
GLY367
3.439
ARG368
3.975
PRO370
3.654
VAL391
4.449
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance. Mol Cancer Ther. 2022 Jan;21(1):3-15. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.