Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T01148 | Target Info | |||
| Target Name | HUMAN NF-kappa-B-activating kinase (TBK1) | ||||
| Synonyms | TANK-binding kinase 1; T2K; Serine/threonine-protein kinase TBK1; NAK | ||||
| Gene Name | TBK1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | BX-795 | Ligand Info | |||
| Canonical SMILES | C1CCN(C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)NCCCNC(=O)C4=CC=CS4)I | ||||
| InChI | 1S/C23H26IN7O2S/c24-18-15-27-22(30-20(18)25-9-5-10-26-21(32)19-8-4-13-34-19)28-16-6-3-7-17(14-16)29-23(33)31-11-1-2-12-31/h3-4,6-8,13-15H,1-2,5,9-12H2,(H,26,32)(H,29,33)(H2,25,27,28,30) | ||||
| InChIKey | VAVXGGRQQJZYBL-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 10077147 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6O8B Crystal structure of STING CTD in complex with TBK1 | ||||||
| Method | X-ray diffraction | Resolution | 3.40 Å | Mutation | Yes | [1] |
| PDB Sequence |
PGLDGICQST
4 SNHLWLLSDI14 LGQGATANVF24 RGRHKKTGDL34 FAIKVFNNIS44 FLRPVDVQMR 54 EFEVLKKLNH64 KNIVKLFAIE74 EETTTRHKVL84 IMEFCPCGSL94 YTVLEEPSNA 104 YGLPESEFLI114 VLRDVVGGMN124 HLRENGIVHR134 NIKPGNIMRV144 IGEDGQSVYK 154 LTDFGAAREL164 EDDEQFVELY174 GTEEYLHPDM184 YERAVLRKDH194 QKKYGATVDL 204 WSIGVTFYHA214 ATGSLPFRPF224 EGPRRNKEVM234 YKIITGKPSG244 AISGVQKAEN 254 GPIDWSGDMP264 VSCSLSRGLQ274 VLLTPVLANI284 LEADQEKCWG294 FDQFFAETSD 304 ILHRMVIHVF314 SLQQMTAHKI324 YIHSYNTATI334 FHELVYKQTK344 IISSNQELIY 354 EGRRLVLEPG364 RLAQHFPKTT374 EENPIFVVSR384 EPLDTIGLIY394 EKISLPKVHP 404 RYDLDGDASM414 AKAITGVVCY424 ACRIASTLLL434 YQELMRKGIR444 WLIELIKDDY 454 NETVHKKTEV464 VITLDFCIRN474 IEKTVKVYEK484 LAAELGEISD500 IHTKLLRLSS 510 SQGTIETSLQ520 DIDSRLSPGG530 SLADAWAHQE540 GTHPKDRNVE550 KLQVLLNCMT 560 EIYYQFKKDQ570 AERRLAYNEE580 QIHKFDKQKL590 YYHATKAMTH600 FTDECVKKYE 610 AFLNKSEEWI620 RKMLHLRKQL630 LSLTNQCFDI640 EEEVSKYQEY650 TNELQE |
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|
|
LEU15
3.401
GLY16
4.205
GLN17
3.099
GLY18
4.068
ALA21
3.881
VAL23
3.884
ALA36
3.451
LYS38
3.291
VAL68
4.426
MET86
3.680
GLU87
3.656
PHE88
3.445
|
|||||
| PDB ID: 4IM2 Structure of Tank-Binding Kinase 1 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [2] |
| PDB Sequence |
GSMQSTSNHL
8 WLLSDILGQG18 ATANVFRGRH28 KKTGDLFAIK38 VFNNRPVDVQ52 MREFEVLKKL 62 NHKNIVKLFA72 IEEETTTRHK82 VLIMEFCPCG92 SLYTVLEEPS102 NAYGLPESEF 112 LIVLRDVVGG122 MNHLRENGIV132 HRNIKPGNIM142 RVIGEDGQSV152 YKLTDFGTEE 178 YLHPDMYERV189 LRKDHATVDL204 WSIGVTFYHA214 ATGSLPFRPF224 EGPRRNKEVM 234 YKIITGKPSG244 AISGVQKAEN254 GPIDWSGDMP264 VSCSLSRGLQ274 VLLTPVLANI 284 LEADQEKCWG294 FDQFFAETSD304 ILHRMVIHVF314 SLQQMTAHKI324 YIHSYNTATI 334 FHELVYKQTK344 IISSNQELIY354 EGRRLVLEPG364 RLAQHFPKTT374 EENPIFVVSR 384 EPLNTIGLIY394 EKISLPKVHP404 RYDLDGDASM414 AKAITGVVCY424 ACRIASTLLL 434 YQELMRKGIR444 WLIELIKDDY454 NETVHKKTEV464 VITLDFCIRN474 IEKTVMGEIS 499 DIHTKLLRLS509 SSQGTIETSL519 QDIDSRLSPG529 GSLADAWAHQ539 EGTHPKDRNV 549 EKLQVLLNCM559 TEIYYQFKKD569 KAERRLAYNE579 EQIHKFDKQK589 LYYHATKAMT 599 HFTDECVKKY609 EAFLNKSEEW619 IRKMLHLRKQ629 LLSLTNQCFD639 IEEEVSKYQE 649 YTNELQET
|
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|
|
LEU15
3.586
GLY16
4.325
GLN17
3.884
GLY18
3.371
ALA21
3.896
VAL23
3.480
ALA36
3.323
LYS38
3.525
VAL68
4.262
MET86
3.607
GLU87
3.109
PHE88
3.620
|
|||||
| PDB ID: 4IM3 Structure of Tank-Binding Kinase 1 | ||||||
| Method | X-ray diffraction | Resolution | 3.34 Å | Mutation | Yes | [2] |
| PDB Sequence |
GSMQSTSNHL
8 WLLSDILGQG18 ATANVFRGRH28 KKTGDLFAIK38 VFNNRPVDVQ52 MREFEVLKKL 62 NHKNIVKLFA72 IEEETTTRHK82 VLIMEFCPCG92 SLYTVLEEPS102 NAYGLPESEF 112 LIVLRDVVGG122 MNHLRENGIV132 HRNIKPGNIM142 RVIGEDGQSV152 YKLTDFGATV 202 DLWSIGVTFY212 HAATGSLPFR222 PFEGPRRNKE232 VMYKIITGKP242 SGAISGVQKA 252 ENGPIDWSGD262 MPVSCSLSRG272 LQVLLTPVLA282 NILEADQEKC292 WGFDQFFAET 302 SDILHRMVIH312 VFSLQQMTAH322 KIYIHSYNTA332 TIFHELVYKQ342 TKIISSNQEL 352 IYEGRRLVLE362 PGRLAQHFPK372 TTEENPIFVV382 SREPLNTIGL392 IYEKISLPKV 402 HPRYDLDGDA412 SMAKAITGVV422 CYACRIASTL432 LLYQELMRKG442 IRWLIELIKD 452 DYNETVHKKT462 EVVITLDFCI472 RNIEKTVKVA492 AELGEISDIH502 TKLLRLSSSQ 512 GTIETSLQDI522 DSRLSPGGSL532 ADAWAHQEGT542 HPKDRNVEKL552 QVLLNCMTEI 562 YYQFKKDKAE572 RRLAYNEEQI582 HKFDKQKLYY592 HATKAMTHFT602 DECVKKYEAF 612 LNKSEEWIRK622 MLHLRKQLLS632 LTNQCFDIEE642 EVSKYQEYTN652 ELQET |
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|
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| PDB ID: 4IWP Crystal structure and mechanism of activation of TBK1 | ||||||
| Method | X-ray diffraction | Resolution | 3.06 Å | Mutation | Yes | [3] |
| PDB Sequence |
AMGQSTSNHL
8 WLLSDILGQG18 ATANVFRGRH28 KKTGDLFAIK38 VFNNISFLRP48 VDVQMREFEV 58 LKKLNHKNIV68 KLFAIEEETT78 TRHKVLIMEF88 CPCGSLYTVL98 EEPSNAYGLP 108 ESEFLIVLRD118 VVGGMNHLRE128 NGIVHRDIKP138 GNIMRVIGED148 GQSVYKLTDF 158 GAARELGTEE178 YLHPDMYEGA200 TVDLWSIGVT210 FYHAATGSLP220 FRPFEGPRRN 230 KEVMYKIITG240 KPSGAISGVQ250 KAENGPIDWS260 GDMPVSCSLS270 RGLQVLLTPV 280 LANILEADQE290 KCWGFDQFFA300 ETSDILHRMV310 IHVFSLQQMT320 AHKIYIHSYN 330 TATIFHELVY340 KQTKIISSNQ350 ELIYEGRRLV360 LEPGRLAQHF370 PKTTEENPIF 380 VVSREPLNTI390 GLIYEKISLP400 KVHPRYDLDG410 DASMAKAITG420 VVCYACRIAS 430 TLLLYQELMR440 KGIRWLIELI450 KDDYNETVHK460 KTEVVITLDF470 CIRNIEKTVK 480 VYAAELGEIS499 DIHTKLLRLS509 SSQGTIETSL519 QDIDSRLSPG529 GSLADAWAHQ 539 EGTHPKDRNV549 EKLQVLLNCM559 TEIYYQFKKD569 KAERRLAYNE579 EQIHKFDKQK 589 LYYHATKAMT599 HFTDECVKKY609 EAFLNKSEEW619 IRKMLHLRKQ629 LLSLTNQCFD 639 IEEEVSKYQE649 YTNELQET
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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 .BX7 or .BX72 or .BX73 or :3BX7;style chemicals stick;color identity;select .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:21 or .A:22 or .A:23 or .A:36 or .A:38 or .A:68 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:92 or .A:93 or .A:96 or .A:139 or .A:140 or .A:142 or .A:156 or .A:157; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE14
3.421
LEU15
3.630
GLY16
4.005
GLN17
4.082
GLY18
3.211
ALA19
4.962
ALA21
3.047
ASN22
4.177
VAL23
3.427
ALA36
3.538
LYS38
2.893
VAL68
4.350
MET86
3.790
|
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| PDB ID: 4IW0 Crystal structure and mechanism of activation of TBK1 | ||||||
| Method | X-ray diffraction | Resolution | 4.00 Å | Mutation | Yes | [3] |
| PDB Sequence |
GSQSTSNHLW
9 LLSDILGQGA19 TANVFRGRHK29 KTGDLFAIKV39 FNNISFLRPV49 DVQMREFEVL 59 KKLNHKNIVK69 LFAIEEETTT79 RHKVLIMEFC89 PCGSLYTVLE99 EPSNAYGLPE 109 SEFLIVLRDV119 VGGMNHLREN129 GIVHRNIKPG139 NIMRVIGEDG149 QSVYKLTDFG 159 AARELEDDEQ169 FVLYGTEEYL180 HPDMYERAVL190 RKDHQKKYGA200 TVDLWSIGVT 210 FYHAATGSLP220 FRPFEGPRRN230 KEVMYKIITG240 KPSGAISGVQ250 KAENGPIDWS 260 GDMPVSCSLS270 RGLQVLLTPV280 LANILEADQE290 KCWGFDQFFA300 ETSDILHRMV 310 IHVFSLQQMT320 AHKIYIHSYN330 TATIFHELVY340 KQTKIISSNQ350 ELIYEGRRLV 360 LEPGRLAQHF370 PKTTEENPIF380 VVSREPLNTI390 GLIYEKISLP400 KVHPRYDLDG 410 DASMAKAITG420 VVCYACRIAS430 TLLLYQELMR440 KGIRWLIELI450 KDDYNETVHK 460 KTEVVITLDF470 CIRNIEKTVK480 VYEKLGEISD500 IHTKLLRLSS510 SQGTIETSLQ 520 DIDSRLSPGG530 SLADAWAHQE540 GTHPKDRNVE550 KLQVLLNCMT560 EIYYQFKKDK 570 AERRLAYNEE580 QIHKFDKQKL590 YYHATKAMTH600 FTDECVKKYE610 AFLNKSEEWI 620 RKMLHLRKQL630 LSLTNQCFDI640 EEEVSKYQEY650 TNELQET
|
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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 .BX7 or .BX72 or .BX73 or :3BX7;style chemicals stick;color identity;select .A:15 or .A:16 or .A:17 or .A:18 or .A:21 or .A:22 or .A:23 or .A:36 or .A:38 or .A:68 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:91 or .A:92 or .A:93 or .A:96 or .A:139 or .A:140 or .A:142 or .A:156 or .A:157; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU15
3.439
GLY16
3.339
GLN17
3.525
GLY18
3.176
ALA21
3.068
ASN22
3.853
VAL23
3.414
ALA36
3.500
LYS38
4.143
VAL68
4.835
MET86
3.896
GLU87
3.474
|
|||||
| PDB ID: 4EUT Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [4] |
| PDB Sequence |
GSQSTSNHLW
9 LLSDILGQGA19 TANVFRGRHK29 KTGDLFAIKV39 FNNISFLRPV49 DVQMREFEVL 59 KKLNHKNIVK69 LFAIEEETTT79 RHKVLIMEFC89 PCGSLYTVLE99 EPSNAYGLPE 109 SEFLIVLRDV119 VGGMNHLREN129 GIVHRNIKPG139 NIMRVIGEDG149 QSVYKLTDFG 159 AARELEDDEQ169 FVSLYGTEEY179 LHPDMYERAV189 LDHQKKYGAT201 VDLWSIGVTF 211 YHAATGSLPF221 RPFEGPRRNK231 EVMYKIITGK241 PSGAISGVQK251 AENGPIDWSG 261 DMPVSCSLSR271 GLQVLLTPVL281 ANILEADQEK291 CWGFDQFFAE301 TSDILHRMVI 311 HVFSLQQMTA321 HKIYIHSYNT331 ATIFHELVYK341 QTKIISSNQE351 LIYEGRRLVL 361 EPGRLAQHFP371 KTTEENPIFV381 VSRE
|
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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 .BX7 or .BX72 or .BX73 or :3BX7;style chemicals stick;color identity;select .A:15 or .A:16 or .A:17 or .A:18 or .A:21 or .A:23 or .A:36 or .A:38 or .A:68 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:91 or .A:92 or .A:96 or .A:139 or .A:140 or .A:142 or .A:156 or .A:157; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU15
3.365
GLY16
3.779
GLN17
3.066
GLY18
3.187
ALA21
3.706
VAL23
3.499
ALA36
3.472
LYS38
4.041
VAL68
4.411
MET86
3.540
GLU87
3.164
|
|||||
| PDB ID: 4EUU Structure of BX-795 Complexed with Human TBK1 Kinase Domain Phosphorylated on Ser172 | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
GSQSTSNHLW
9 LLSDILGQGA19 TANVFRGRHK29 KTGDLFAIKV39 FNNISFLRPV49 DVQMREFEVL 59 KKLNHKNIVK69 LFAIEEETTT79 RHKVLIMEFC89 PCGSLYTVLE99 EPSNAYGLPE 109 SEFLIVLRDV119 VGGMNHLREN129 GIVHRNIKPG139 NIMRVIGEDG149 QSVYKLTDFG 159 AARELEDDEQ169 FVLYGTEEYL180 HPDMYERAVL190 RKDHQKKYGA200 TVDLWSIGVT 210 FYHAATGSLP220 FRPFEGPRRN230 KEVMYKIITG240 KPSGAISGVQ250 KAENGPIDWS 260 GDMPVSCSLS270 RGLQVLLTPV280 LANILEADQE290 KCWGFDQFFA300 ETSDILH |
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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 .BX7 or .BX72 or .BX73 or :3BX7;style chemicals stick;color identity;select .A:15 or .A:16 or .A:17 or .A:18 or .A:21 or .A:22 or .A:23 or .A:36 or .A:38 or .A:68 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:91 or .A:92 or .A:93 or .A:95 or .A:96 or .A:139 or .A:140 or .A:142 or .A:156 or .A:157; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU15
2.719
GLY16
3.775
GLN17
3.531
GLY18
3.610
ALA21
3.539
ASN22
4.768
VAL23
3.716
ALA36
3.479
LYS38
3.519
VAL68
4.086
MET86
3.596
GLU87
3.276
PHE88
3.548
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1. Nature. 2019 May;569(7758):718-722. | ||||
| REF 2 | Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell Rep. 2013 Mar 28;3(3):747-58. | ||||
| REF 3 | Crystal structure and mechanism of activation of TANK-binding kinase 1. Cell Rep. 2013 Mar 28;3(3):734-46. | ||||
| REF 4 | Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9378-83. | ||||
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