Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T15636 | Target Info | |||
| Target Name | Tau-tubulin kinase (TTBK1) | ||||
| Synonyms | Tau-tubulin kinase 1; KIAA1855; Brain-derived tau kinase; BDTK | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | TTBK1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline | Ligand Info | |||||
| Structure Description | TTBK1 in complex with inhibitor | PDB:4BTK | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
DILPANYVVK
55 DRWKVLKKIG65 GGEIYEAMDL78 LTRENVALKV88 ESAQQPKQVL98 KMEVAVLKKL 108 QGKDHVCRFI118 GCGRNEKFNY128 VVMQLQGRNL138 ADLRRSQPRG148 TFTLSTTLRL 158 GKQILESIEA168 IHSVGFLHRD178 IKPSNFAMGR188 LPSTYRKCYM198 LDFGLARQYT 208 NTTGDVRPPR218 NVAGFRGTVR228 YASVNAHKNR238 EMGRHDDLWS248 LFYMLVEFAV 258 GQLPWRKIKD268 KEQVGMIKEK278 YEHRMLLKHM288 PSEFHLFLDH298 IASLDYFTKP 308 DYQLIMSVFE318 NSMKERGIAE328 NEAFDWE
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | TTBK1 in complex with ATP | PDB:4BTJ | ||||
| Method | X-ray diffraction | Resolution | 2.16 Å | Mutation | No | [1] |
| PDB Sequence |
ADILPANYVV
54 KDRWKVLKKI64 GGGGFGEIYE74 AMDLLTRENV84 ALKVESAQQP94 KQVLKMEVAV 104 LKKLQGKDHV114 CRFIGCGRNE124 KFNYVVMQLQ134 GRNLADLRRS144 QPRGTFTLST 154 TLRLGKQILE164 SIEAIHSVGF174 LHRDIKPSNF184 AMGRLPSTYR194 KCYMLDFGLA 204 RQYTNTTGDV214 RPPRNVAGFR224 GTVRYASVNA234 HKNREMGRHD244 DLWSLFYMLV 254 EFAVGQLPWR264 KIKDKEQVGM274 IKEKYEHRML284 LKHMPSEFHL294 FLDHIASLDY 304 FTKPDYQLIM314 SVFENSMKER324 GIAENEAFDW334 EK
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ILE64
3.529
GLY65
3.571
GLY66
3.159
GLY67
4.515
GLY68
3.338
PHE69
4.994
GLY70
4.589
ILE72
3.491
ALA85
3.389
LYS87
2.708
GLU101
4.862
CYS115
3.725
|
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| Ligand Name: Methyl 2-Bromo-5-(7h-Pyrrolo[2,3-D]pyrimidin-4-Ylamino)benzoate | Ligand Info | |||||
| Structure Description | TTBK1 in complex with inhibitor | PDB:4BTM | ||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [1] |
| PDB Sequence |
ADILPANYVV
54 KDRWKVLKKI64 GGGGFGEIYE74 AMDLLTRENV84 ALKVESAQQP94 KQVLKMEVAV 104 LKKLQGKDHV114 CRFIGCGRNE124 KFNYVVMQLQ134 GRNLADLRRS144 QPRGTFTLST 154 TLRLGKQILE164 SIEAIHSVGF174 LHRDIKPSNF184 AMGRLPSTYR194 KCYMLDFGLA 204 RQYTNTTGDV214 RPPRNVAGFR224 GTVRYASVNA234 HKNREMGRHD244 DLWSLFYMLV 254 EFAVGQLPWR264 KIKDKEQVGM274 IKEKYEHRML284 LKHMPSEFHL294 FLDHIASLDY 304 FTKPDYQLIM314 SVFENSMKER324 GIAENEAFDW334 EK
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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 .F8E or .F8E2 or .F8E3 or :3F8E;style chemicals stick;color identity;select .A:64 or .A:65 or .A:66 or .A:72 or .A:85 or .A:87 or .A:115 or .A:131 or .A:132 or .A:133 or .A:134 or .A:135 or .A:137 or .A:180 or .A:182 or .A:183 or .A:199; 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-(2-Amino-5,6,7,8-tetrahydropyrimido[4',5':3,4]cyclohepta[1,2-b]indol-11-yl)-2-methylbut-3-yn-2-ol | Ligand Info | |||||
| Structure Description | Structure of TTBK1 kinase domain in complex with Compound 3 | PDB:7JXX | ||||
| Method | X-ray diffraction | Resolution | 1.56 Å | Mutation | No | [2] |
| PDB Sequence |
DILPANYVVK
31 DRWKVLKKIG41 GGFGEIYEAM52 DLLTRENVAL62 KVESAQQPKQ72 VLKMEVAVLK 82 KLQGKDHVCR92 FIGCGRNEKF102 NYVVMQLQGR112 NLADLRRSQP122 RGTFTLSTTL 132 RLGKQILESI142 EAIHSVGFLH152 RDIKPSNFAM162 GRLPSTYRKC172 YMLDFGLARQ 182 YTNTDVRPPR194 NVAGFRGTVR204 YASVNAHKNR214 EMGRHDDLWS224 LFYMLVEFAV 234 GQLPWRKIKD244 KEQVGMIKEK254 YEHRMLLKHM264 PSEFHLFLDH274 IASLDYFTKP 284 DYQLIMSVFE294 NSMKERGIAE304 NEAFDWEK
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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 .VP7 or .VP72 or .VP73 or :3VP7;style chemicals stick;color identity;select .A:40 or .A:41 or .A:48 or .A:61 or .A:63 or .A:77 or .A:81 or .A:91 or .A:105 or .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:175 or .A:176 or .A:177 or .A:178; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: (3S)-1-[1-(2-aminopyrimidin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol | Ligand Info | |||||
| Structure Description | Structure of TTBK1 kinase domain in complex with Compound 18 | PDB:7JXY | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [2] |
| PDB Sequence |
ILPANYVVKD
32 RWKVLKKIGG42 GGFGEIYEAM52 DLLTRENVAL62 KVESAQQPKQ72 VLKMEVAVLK 82 KLQGKDHVCR92 FIGCGRNEKF102 NYVVMQLQGR112 NLADLRRSQP122 RGTFTLSTTL 132 RLGKQILESI142 EAIHSVGFLH152 RDIKPSNFAM162 GRLPSTYRKC172 YMLDFGLARQ 182 YTNTTGDVRP192 PRNVAGFRGT202 VRYASVNAHK212 NREMGRHDDL222 WSLFYMLVEF 232 AVGQLPWRKI242 KDKEQVGMIK252 EKYEHRMLLK262 HMPSEFHLFL272 DHIASLDYFT 282 KPDYQLIMSV292 FENSMKERGI302 AENEAFDWEK312
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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 .VSY or .VSY2 or .VSY3 or :3VSY;style chemicals stick;color identity;select .A:40 or .A:41 or .A:48 or .A:61 or .A:63 or .A:74 or .A:77 or .A:81 or .A:91 or .A:105 or .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:158 or .A:159 or .A:174 or .A:175 or .A:176 or .A:177 or .A:178; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE40
3.896
GLY41
4.576
ILE48
3.212
ALA61
3.338
LYS63
3.662
LEU74
4.763
GLU77
2.138
LEU81
3.906
CYS91
3.882
VAL105
3.667
MET107
3.340
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| Ligand Name: 3-({5-[(4-Amino-4-Methylpiperidin-1-Yl)methyl]pyrrolo[2,1-F][1,2,4]triazin-4-Yl}amino)-5-Bromophenol | Ligand Info | |||||
| Structure Description | Human tau tubulin kinase 1 (TTBK1) complexed with 3-({5-[(4-amino-4-methylpiperidin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)-5-bromophenol | PDB:4NFN | ||||
| Method | X-ray diffraction | Resolution | 1.42 Å | Mutation | No | [3] |
| PDB Sequence |
DILPANYVVK
31 DRWKVLKKIG41 GGGFGEIYEA51 MDLLTRENVA61 LKVESAQQPK71 QVLKMEVAVL 81 KKLQGKDHVC91 RFIGCGRNEK101 FNYVVMQLQG111 RNLADLRRSQ121 PRGTFTLSTT 131 LRLGKQILES141 IEAIHSVGFL151 HRDIKPSNFA161 MGRLPSTYRK171 CYMLDFGLAR 181 QYTNTTGDVR191 PPRNVAGFRG201 TVRYASVNAH211 KNREMGRHDD221 LWSLFYMLVE 231 FAVGQLPWRK241 IKDKEQVGMI251 KEKYEHRMLL261 KHMPSEFHLF271 LDHIASLDYF 281 TKPDYQLIMS291 VFENSMKERG301 IAENEAFDWE311 KAG
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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 .2KC or .2KC2 or .2KC3 or :32KC;style chemicals stick;color identity;select .A:40 or .A:41 or .A:42 or .A:48 or .A:61 or .A:62 or .A:63 or .A:77 or .A:91 or .A:105 or .A:106 or .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:156 or .A:158 or .A:159 or .A:175 or .A:176 or .A:177 or .A:178; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE40
3.163
GLY41
3.260
GLY42
4.074
ILE48
2.965
ALA61
2.767
LEU62
4.151
LYS63
3.117
GLU77
1.797
CYS91
3.459
VAL105
3.567
VAL106
4.595
MET107
3.211
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| Ligand Name: N-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine | Ligand Info | |||||
| Structure Description | Crystal structure of TTBK1 in complex with VNG1.35 (compound 23) | PDB:7Q8W | ||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | No | [4] |
| PDB Sequence |
ADILPANYVV
30 KDRWKVLKKI40 GGGGFGEIYE50 AMDLLTRENV60 ALKVESAQQP70 KQVLKMEVAV 80 LKKLQGKDHV90 CRFIGCGRNE100 KFNYVVMQLQ110 GRNLADLRRS120 QPRGTFTLST 130 TLRLGKQILE140 SIEAIHSVGF150 LHRDIKPSNF160 AMGRLPSTYR170 KCYMLDFGLA 180 RQYTNTTGDV190 RPPRNVAGFR200 GTVRYASVNA210 HKNREMGRHD220 DLWSLFYMLV 230 EFAVGQLPWR240 KIKDKEQVGM250 IKEKYEHRML260 LKHMPSEFHL270 FLDHIASLDY 280 FTKPDYQLIM290 SVFENSMKER300 GIAENEAFDW310 EK
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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 .9IO or .9IO2 or .9IO3 or :39IO;style chemicals stick;color identity;select .A:40 or .A:41 or .A:48 or .A:61 or .A:63 or .A:91 or .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:113 or .A:116 or .A:158 or .A:175; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: N-[4-(2-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine | Ligand Info | |||||
| Structure Description | Crystal structure of TTBK1 in complex with VNG2.73 (compound 42) | PDB:7Q8V | ||||
| Method | X-ray diffraction | Resolution | 2.13 Å | Mutation | No | [4] |
| PDB Sequence |
ADILPANYVV
30 KDRWKVLKKI40 GGGGFGEIYE50 AMDLLTRENV60 ALKVESAQQP70 KQVLKMEVAV 80 LKKLQGKDHV90 CRFIGCGRNE100 KFNYVVMQLQ110 GRNLADLRRS120 QPRGTFTLST 130 TLRLGKQILE140 SIEAIHSVGF150 LHRDIKPSNF160 AMGRLPSTYR170 KCYMLDFGLA 180 RQYTNTTGDV190 RPPRNVAGFR200 GTVRYASVNA210 HKNREMGRHD220 DLWSLFYMLV 230 EFAVGQLPWR240 KIKDKEQVGM250 IKEKYEHRML260 LKHMPSEFHL270 FLDHIASLDY 280 FTKPDYQLIM290 SVFENSMKER300 GIAENEAFDW310 EK
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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 .9IV or .9IV2 or .9IV3 or :39IV;style chemicals stick;color identity;select .A:40 or .A:41 or .A:48 or .A:61 or .A:63 or .A:91 or .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:113 or .A:115 or .A:116 or .A:119 or .A:158 or .A:175; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | X-ray structural analysis of tau-tubulin kinase?1 and its interactions with small molecular inhibitors. ChemMedChem. 2013 Nov;8(11):1846-54. | ||||
| REF 2 | Discovery of Potent and Brain-Penetrant Tau Tubulin Kinase 1 (TTBK1) Inhibitors that Lower Tau Phosphorylation In Vivo. J Med Chem. 2021 May 13;64(9):6358-6380. | ||||
| REF 3 | The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor. Acta Crystallogr F Struct Biol Commun. 2014 Feb;70(Pt 2):173-81. | ||||
| REF 4 | TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy. J Med Chem. 2022 Jan 27;65(2):1585-1607. | ||||
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