Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T03279 | Target Info | |||
| Target Name | Ribosomal protein S6 kinase alpha-3 (RSK3) | ||||
| Synonyms | pp90RSK2; p90RSK3; p90-RSK 3; S6K-alpha-3; Ribosomal S6 kinase 2; RSK2; RSK-2; MAPKAPK1B; MAPKAPK-1b; MAPKAP kinase 1b; MAPK-activated protein kinase 1b; MAP kinase-activated protein kinase 1b; Insulin-stimulated protein kinase 1; ISPK1; ISPK-1; 90 kDa ribosomal protein S6 kinase 3 | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | RPS6KA3 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | RSK2 N-terminal kinase domain in complex with ORF45 | PDB:7OPO | ||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | No | [1] |
| PDB Sequence |
VSIKEIAITH
54 HVKEGHEKAD64 PSQFELLKVL74 GQGSFGKVFL84 VKKISGSDAR94 QLYAMKVLKK 104 ATLKVRDRDI121 LVEVNHPFIV131 KLHYAFQTEG141 KLYLILDFLR151 GGDLFTRLSK 161 EVMFTEEDVK171 FYLAELALAL181 DHLHSLGIIY191 RDLKPENILL201 DEEGHIKLTD 211 FGLSKESIDH221 EKKAYSFTVE233 YMAPEVVNRR243 GHTQSADWWS253 FGVLMFEMLT 263 GTLPFQGKDR273 KETMTMILKA283 KLGMPQFLSP293 EAQSLLRMLF303 KRNPANRLGA 313 GPDGVEEIKR323 HSFFSTIDWN333 KLYRREIHPP343 FKPAT
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LEU74
3.633
GLY75
3.700
GLN76
3.868
GLY77
3.560
SER78
2.870
PHE79
3.303
GLY80
4.377
VAL82
3.477
ALA98
3.279
LYS100
2.932
VAL131
4.123
LEU147
4.312
|
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| Ligand Name: (2s)-2-Cyano-3-(1h-Indazol-5-Yl)propanamide | Ligand Info | |||||
| Structure Description | RSK2 CTD bound to 2-cyano-3-(1H-indazol-5-yl)acrylamide | PDB:4JG6 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [2] |
| PDB Sequence |
SIVQQLHRNS
415 IQFTDGYEVK425 EDISVCKRCI440 HKATNMEFAV450 KIIDKSKRDP460 TEEIEILLRY 470 GQHPNIITLK480 DVYDDGKYVY490 VVTELMKGGE500 LLDKILRQKF510 FSEREASAVL 520 FTITKTVEYL530 HAQGVVHRDL540 KPSNILYVDE550 SGNPESIRIC560 DFGFAKQLRA 570 ENGLLMTPCY580 TANFVAPEVL590 ERQGYDAACD600 IWSLGVLLYT610 MLTGYTPFAN 620 GPDDTPEEIL630 ARIGSGKFSL640 SGGYWNSVSD650 TAKDLVSKML660 HVDPHQRLTA 670 ALVLRHPWIV680 HWDQLPQYQL690 NRQDAPHLVK700 GAMAATYSAL710 NR |
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| Ligand Name: (2r)-2-Cyano-3-[3-(1h-Pyrrolo[2,3-B]pyridin-3-Ylcarbonyl)phenyl]propanamide | Ligand Info | |||||
| Structure Description | Structure of RSK2 CTD bound to 3-(3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl)-2-cyanoacrylamide | PDB:4JG7 | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [2] |
| PDB Sequence |
HSIVQQLHRN
414 SIQFTDGYEV424 KEDIGVYSVC436 KRCIHKATNM446 EFAVKIIDKS456 KRDPTEEIEI 466 LLRYGQHPNI476 ITLKDVYDDG486 KYVYVVTELM496 KGGELLDKIL506 RQKFFSEREA 516 SAVLFTITKT526 VEYLHAQGVV536 HRDLKPSNIL546 YVDESGNPES556 IRICDFGFAK 566 QLRAENGLLM576 TPCYTANFVA586 PEVLERQGYD596 AACDIWSLGV606 LLYTMLTGYT 616 PFANGPDDTP626 EEILARIGSG636 KFSLSGGYWN646 SVSDTAKDLV656 SKMLHVDPHQ 666 RLTAALVLRH676 PWIVHWDQLP686 QYQLNRQDAP696 HLVKGAMAAT706 YSALNRN |
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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 .1LC or .1LC2 or .1LC3 or :31LC;style chemicals stick;color identity;select .A:428 or .A:429 or .A:430 or .A:434 or .A:435 or .A:436 or .A:449 or .A:450 or .A:451 or .A:463 or .A:477 or .A:491 or .A:493 or .A:494 or .A:495 or .A:496 or .A:497 or .A:499 or .A:500 or .A:543 or .A:544 or .A:546 or .A:560 or .A:561 or .A:562; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE428
2.510
GLY429
2.479
VAL430
3.014
SER434
3.672
VAL435
4.919
CYS436
1.850
ALA449
2.273
VAL450
4.276
LYS451
2.473
GLU463
4.923
ILE477
3.211
VAL491
4.852
THR493
2.639
|
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| Ligand Name: (2s)-2-Cyano-N-(1-Hydroxy-2-Methylpropan-2-Yl)-3-[3-(3,4,5-Trimethoxyphenyl)-1h-Indazol-5-Yl]propanamide | Ligand Info | |||||
| Structure Description | Structure of RSK2 T493M CTD mutant bound to 2-cyano-N-(1-hydroxy-2-methylpropan-2-yl)-3-(3-(3,4,5-trimethoxyphenyl)-1H-indazol-5-yl)acrylamide | PDB:4JG8 | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
SIQFTDGYEV
424 KEDIGVGSYS434 VCKRCIHKAT444 NMEFAVKIID454 KSKRDPTEEI464 EILLRYGQHP 474 NIITLKDVYD484 DGKYVYVVME494 LMKGGELLDK504 ILRQKFFSER514 EASAVLFTIT 524 KTVEYLHAQG534 VVHRDLKPSN544 ILYVDESGNP554 ESIRICDFGF564 AKQLRAENGL 574 LMTPCYTANF584 VAPEVLERQG594 YDAACDIWSL604 GVLLYTMLTG614 YTPFANGPDD 624 TPEEILARIG634 SGKFSLSGGY644 WNSVSDTAKD654 LVSKMLHVDP664 HQRLTAALVL 674 RHPWIVHWDQ684 LPQYQLNRQD694 APHLVKGAMA704 ATYSALNRNQ714 |
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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 .1LE or .1LE2 or .1LE3 or :31LE;style chemicals stick;color identity;select .A:428 or .A:429 or .A:430 or .A:431 or .A:432 or .A:433 or .A:434 or .A:435 or .A:436 or .A:449 or .A:451 or .A:463 or .A:477 or .A:493 or .A:494 or .A:495 or .A:496 or .A:497 or .A:498 or .A:499 or .A:500 or .A:539 or .A:541 or .A:543 or .A:544 or .A:546 or .A:560 or .A:561 or .A:562 or .A:563; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE428
2.518
GLY429
3.237
VAL430
4.485
GLY431
2.498
SER432
4.721
TYR433
4.524
SER434
1.942
VAL435
3.823
CYS436
1.806
ALA449
2.528
LYS451
2.288
GLU463
4.462
ILE477
2.674
MET493
2.168
GLU494
2.182
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| Ligand Name: Methyl (2s)-3-{4-Amino-7-[(1e)-3-Hydroxyprop-1-En-1-Yl]-5-(4-Methylphenyl)-7h-Pyrrolo[2,3-D]pyrimidin-6-Yl}-2-Cyanopropanoate | Ligand Info | |||||
| Structure Description | Rsk2 C-terminal Kinase Domain with inhibitor (E)-methyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate | PDB:4D9T | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
SIQFTDGYEV
424 KEDIGVGSYS434 VCKRCIHKAT444 NMEFAVKIID454 KSKRDPTEEI464 EILLRYGQHP 474 NIITLKDVYD484 DGKYVYVVTE494 LMKGGELLDK504 ILRQKFFSER514 EASAVLFTIT 524 KTVEYLHAQG534 VVHRDLKPSN544 ILYVDESGNP554 ESIRICDFGF564 AKQLRAENGL 574 LMTPCYTANF584 VAPEVLERQG594 YDAACDIWSL604 GVLLYTMLTG614 YTPFANGPDD 624 TPEEILARIG634 SGKFSLSGGY644 WNSVSDTAKD654 LVSKMLHVDP664 HQRLTAALVL 674 RHPWIVHWDQ684 LPQYQLNRQD694 APHLVKGAMA704 ATYSALNRN
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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 .0JG or .0JG2 or .0JG3 or :30JG;style chemicals stick;color identity;select .A:428 or .A:429 or .A:430 or .A:431 or .A:434 or .A:435 or .A:436 or .A:449 or .A:450 or .A:451 or .A:463 or .A:467 or .A:477 or .A:491 or .A:493 or .A:494 or .A:495 or .A:496 or .A:543 or .A:544 or .A:546 or .A:560 or .A:561; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE428
3.019
GLY429
4.608
VAL430
4.907
GLY431
4.977
SER434
3.472
VAL435
4.864
CYS436
2.260
ALA449
2.984
VAL450
4.456
LYS451
3.298
GLU463
4.358
LEU467
3.950
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| Ligand Name: Tert-Butyl (2s)-3-[4-Amino-7-(3-Hydroxypropyl)-5-(4-Methylphenyl)-7h-Pyrrolo[2,3-D]pyrimidin-6-Yl]-2-Cyanopropanoate | Ligand Info | |||||
| Structure Description | Rsk2 C-terminal Kinase Domain, (E)-tert-butyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate | PDB:4D9U | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [3] |
| PDB Sequence |
VQQLHRNSIQ
417 FTDGYEVKED427 IGVGSYSVCK437 RCIHKATNME447 FAVKIIDKSK457 RDPTEEIEIL 467 LRYGQHPNII477 TLKDVYDDGK487 YVYVVTELMK497 GGELLDKILR507 QKFFSEREAS 517 AVLFTITKTV527 EYLHAQGVVH537 RDLKPSNILY547 VDESGNPESI557 RICDFGFAKQ 567 LRAENGLLMT577 PCYTANFVAP587 EVLERQGYDA597 ACDIWSLGVL607 LYTMLTGYTP 617 FANGPDDTPE627 EILARIGSGK637 FSLSGGYWNS647 VSDTAKDLVS657 KMLHVDPHQR 667 LTAALVLRHP677 WIVHWDQLPQ687 YQLNRQDAPH697 LVKGAMAATY707 SALNRNQ |
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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 .0JH or .0JH2 or .0JH3 or :30JH;style chemicals stick;color identity;select .A:428 or .A:429 or .A:430 or .A:431 or .A:434 or .A:435 or .A:436 or .A:449 or .A:450 or .A:451 or .A:463 or .A:467 or .A:477 or .A:491 or .A:493 or .A:494 or .A:495 or .A:496 or .A:543 or .A:544 or .A:546 or .A:560 or .A:561; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE428
3.116
GLY429
3.359
VAL430
3.649
GLY431
3.465
SER434
2.901
VAL435
3.486
CYS436
1.952
ALA449
3.198
VAL450
4.477
LYS451
3.322
GLU463
4.108
LEU467
3.503
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| Ligand Name: (7r)-2-[(3,5-Difluoro-4-Hydroxyphenyl)amino]-5,7-Dimethyl-8-(3-Methylbutyl)-7,8-Dihydropteridin-6(5h)-One | Ligand Info | |||||
| Structure Description | Rsk2 N-terminal Kinase in Complex with BI-D1870 | PDB:5D9K | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [4] |
| PDB Sequence |
KADPSQFELL
71 KVLGQGSFGK81 VFLVKKISGS91 DARQLYAMKV101 LKKATLKVRD111 RVRTKMERDI 121 LVEVNHPFIV131 KLHYAFQTEG141 KLYLILDFLR151 GGDLFTRLSK161 EVMFTEEDVK 171 FYLAELALAL181 DHLHSLGIIY191 RDLKPENILL201 DEEGHIKLTD211 FGLSKCGTVE 233 YMAPEVVNRR243 GHTQSADWWS253 FGVLMFEMLT263 GTLPFQGKDR273 KETMTMILKA 283 KLGMPQFLSP293 EAQSLLRMLF303 KRNPANRLGA313 GPDGVEEIKR323 HSFFSTIDWN 333 KLYRREIHPP343 FKPATFYFDP359
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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 .584 or .5842 or .5843 or :3584;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:79 or .A:82 or .A:98 or .A:100 or .A:131 or .A:147 or .A:148 or .A:149 or .A:150 or .A:154 or .A:200 or .A:210 or .A:211 or .A:212; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-(1h-Benzimidazol-7-Yl)-N-(3,4,5-Trimethoxyphenyl)-1,3-Benzoxazol-2-Amine | Ligand Info | |||||
| Structure Description | Rsk2 N-terminal kinase in complex with 2-amino-7-substituted benzoxazole compound 27 | PDB:4NW6 | ||||
| Method | X-ray diffraction | Resolution | 1.74 Å | Mutation | No | [5] |
| PDB Sequence |
AITHHVKEGH
60 EKADPSQFEL70 LKVLGQGSFG80 KVFLVKKISG90 SDARQLYAMK100 VLKKATLKVR 110 DRVRTKMERD120 ILVEVNHPFI130 VKLHYAFQTE140 GKLYLILDFL150 RGGDLFTRLS 160 KEVMFTEEDV170 KFYLAELALA180 LDHLHSLGII190 YRDLKPENIL200 LDEEGHIKLT 210 DFGLSKESID220 HEKKAYSFCG230 TVEYMAPEVV240 NRRGHTQSAD250 WWSFGVLMFE 260 MLTGTLPFQG270 KDRKETMTMI280 LKAKLGMPQF290 LSPEAQSLLR300 MLFKRNPANR 310 LGAGPDGVEE320 IKRHSFFSTI330 DWNKLYRREI340 HPPFKPTFYF357 DP |
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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 .2NS or .2NS2 or .2NS3 or :32NS;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:98 or .A:131 or .A:147 or .A:148 or .A:149 or .A:150 or .A:151 or .A:152 or .A:153 or .A:154 or .A:197 or .A:198 or .A:200 or .A:210 or .A:211; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-(2-Fluoro-6-Methoxyphenyl)-N-(3,4,5-Trimethoxyphenyl)-1,3-Benzoxazol-2-Amine | Ligand Info | |||||
| Structure Description | Rsk2 N-terminal kinase in complex with 2-amino-7-substituted benzoxazole compound 8 | PDB:4NW5 | ||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | No | [5] |
| PDB Sequence |
AITHHVKEGH
60 EKADPSQFEL70 LKVLGQGSFG80 KVFLVKKISG90 SDARQLYAMK100 VLKKATLKVR 110 DRVRTKMERD120 ILVEVNHPFI130 VKLHYAFQTE140 GKLYLILDFL150 RGGDLFTRLS 160 KEVMFTEEDV170 KFYLAELALA180 LDHLHSLGII190 YRDLKPENIL200 LDEEGHIKLT 210 DFGLSKESID220 HEKKAYSFCG230 TVEYMAPEVV240 NRRGHTQSAD250 WWSFGVLMFE 260 MLTGTLPFQG270 KDRKETMTMI280 LKAKLGMPQF290 LSPEAQSLLR300 MLFKRNPANR 310 LGAGPDGVEE320 IKRHSFFSTI330 DWNKLYRREI340 HPPFKPTFYF357 DP |
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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 .2NR or .2NR2 or .2NR3 or :32NR;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:98 or .A:131 or .A:147 or .A:148 or .A:149 or .A:150 or .A:151 or .A:152 or .A:153 or .A:154 or .A:197 or .A:198 or .A:200 or .A:210 or .A:211; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4,4'-(1h-Pyrazole-3,4-Diyl)diphenol | Ligand Info | |||||
| Structure Description | Rsk2 N-terminal Kinase in Complex with bis-phenol pyrazole | PDB:5D9L | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [4] |
| PDB Sequence |
EIAITHHVKE
58 GHEKADPSQF68 ELLKVLGQGS78 FGKVFLVKKI88 SGSDARQLYA98 MKVLKKATLK 108 VRDRVRTKME118 RDILVEVNHP128 FIVKLHYAFQ138 TEGKLYLILD148 FLRGGDLFTR 158 LSKEVMFTEE168 DVKFYLAELA178 LALDHLHSLG188 IIYRDLKPEN198 ILLDEEGHIK 208 LTDFGLSKEG230 TVEYMAPEVV240 NRRGHTQSAD250 WWSFGVLMFE260 MLTGTLPFQG 270 KDRKETMTMI280 LKAKLGMPQF290 LSPEAQSLLR300 MLFKRNPANR310 LGAGPDGVEE 320 IKRHSFFSTI330 DWNKLYRREI340 HPPFKPATGR350 PEDTFYFDP
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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 .583 or .5832 or .5833 or :3583;style chemicals stick;color identity;select .A:74 or .A:75 or .A:79 or .A:82 or .A:98 or .A:100 or .A:131 or .A:147 or .A:148 or .A:149 or .A:150 or .A:200 or .A:210 or .A:211 or .A:212; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2,6-Difluoro-4-[4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol | Ligand Info | |||||
| Structure Description | Rsk2 N-terminal kinase in complex with LJH685 | PDB:4NUS | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [6] |
| PDB Sequence |
THHVKEGHEK
62 ADPSQFELLK72 VLGQGSFGKV82 FLVKKISGSD92 ARQLYAMKVL102 KKATLKVRDR 112 VRTKMERDIL122 VEVNHPFIVK132 LHYAFQTEGK142 LYLILDFLRG152 GDLFTRLSKE 162 VMFTEEDVKF172 YLAELALALD182 HLHSLGIIYR192 DLKPENILLD202 EEGHIKLTDF 212 GLSKESIDHE222 KKAYSFCGTV232 EYMAPEVVNR242 RGHTQSADWW252 SFGVLMFEML 262 TGTLPFQGKD272 RKETMTMILK282 AKLGMPQFLS292 PEAQSLLRML302 FKRNPANRLG 312 AGPDGVEEIK322 RHSFFSTIDW332 NKLYRREIHP342 PFKPATFYFD358 P |
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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 .2NK or .2NK2 or .2NK3 or :32NK;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:79 or .A:82 or .A:98 or .A:100 or .A:131 or .A:147 or .A:148 or .A:149 or .A:150 or .A:200 or .A:210 or .A:211 or .A:212; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host. Nat Commun. 2022 Jan 25;13(1):472. | ||||
| REF 2 | Electrophilic fragment-based design of reversible covalent kinase inhibitors. J Am Chem Soc. 2013 Apr 10;135(14):5298-301. | ||||
| REF 3 | Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles. Nat Chem Biol. 2012 Apr 1;8(5):471-6. | ||||
| REF 4 | Discovery of Potent and Selective RSK Inhibitors as Biological Probes. J Med Chem. 2015 Sep 10;58(17):6766-83. | ||||
| REF 5 | 2-Amino-7-substituted benzoxazole analogs as potent RSK2 inhibitors. Bioorg Med Chem Lett. 2014 Mar 15;24(6):1592-6. | ||||
| REF 6 | Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers. Mol Cancer Res. 2014 May;12(5):803-12. | ||||
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