Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T00852 | Target Info | |||
| Target Name | Serine/threonine-protein kinase cot (COT) | ||||
| Synonyms | Tumor progression locus 2; TPL-2; Proto-oncogene c-Cot; Mitogen-activated protein kinase kinase kinase 8; ESTF; Cancer Osaka thyroid oncogene; COT | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MAP3K8 | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 5-[5-(1h-Indol-3-Yl)-1h-Pyrrolo[2,3-B]pyridin-3-Yl]-1,3,4-Oxadiazol-2-Amine | Ligand Info | |||||
| Structure Description | Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine | PDB:4Y85 | ||||
| Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | No | [1] |
| PDB Sequence |
LSSVRYGTVE
82 DLLAFANHIS92 NTPQESGILL110 NMVITPQNGR120 YQIDSDVLLI130 PWKLTYRNIF 143 IPRGAFGKVY153 LAQDIKTKKR163 MACKLIPVDQ173 FKPSDVEIQA183 CFRHENIAEL 193 YGAVLWGETV203 HLFMEAGEGG213 SVLEKLESCG223 PMREFEIIWV233 TKHVLKGLDF 243 LHSKKVIHHD253 IKPSNIVFMS263 TKAVLVDFGL273 SVQMTEDVYF283 PKDLRGTEIY 293 MSPEVILCRG303 HSTKADIYSL313 GATLIHMQTG323 TPPWVKRYPR333 SAYPSYLYII 343 HKQAPPLEDI353 ADDCSPGMRE363 LIEASLERNP373 NHRPRAADLL383 KHEALNP |
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|
|
TRP132
3.489
PHE143
3.795
PRO145
3.370
ARG146
4.751
GLY147
3.381
ALA148
4.848
VAL152
3.410
ALA165
3.253
LYS167
2.885
ALA191
4.671
MET207
3.725
GLU208
2.809
|
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| Ligand Name: N-[2-(Morpholin-4-Yl)ethyl]-6-(8-Phenyl-1h-Imidazo[4,5-C][1,7]naphthyridin-1-Yl)-1,3-Benzothiazol-2-Amine | Ligand Info | |||||
| Structure Description | Discovery of imidazoquinolines as a novel class of potent, selective and in vivo efficacious COT kinase inhibitors | PDB:5IU2 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
LSSVRYGTVE
82 DLLAFANHIS92 NFYGQRPQES106 GILLNMVITP116 QNGRYQIDSD126 VLLIPWKLTY 136 RNGSDFIPRG147 AFGKVYLAQD157 IKTKKRMACK167 LIPVDQFKPS177 DVEIQACFRH 187 ENIAELYGAV197 LWGETVHLFM207 EAGEGGSVLE217 KLESCGPMRE227 FEIIWVTKHV 237 LKGLDFLHSK247 KVIHHDIKPS257 NIVFMSTKAV267 LVDFGLSVQM277 TEDVYFPKDL 287 RGTEIYMSPE297 VILCRGHSTK307 ADIYSLGATL317 IHMQTGTPPW327 VKRYPRSAYP 337 SYLYIIHKQA347 PPLEDIADDC357 SPGMRELIEA367 SLERNPNHRP377 RAADLLKHEA 387 LN
|
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|
|
TRP132
3.389
LYS133
4.946
LEU134
3.531
TYR136
4.527
PRO145
4.311
ALA148
4.157
PHE149
3.250
GLY150
3.383
LYS151
4.427
VAL152
3.560
ALA165
3.433
LYS167
3.565
|
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| Ligand Name: 5-[2-Amino-5-(Quinolin-3-Yl)pyridin-3-Yl]-1,3,4-Oxadiazole-2(3h)-Thione | Ligand Info | |||||
| Structure Description | Crystal structure of COT kinase domain in complex with 5-(2-amino-5-(quinolin-3-yl)pyridin-3-yl)-1,3,4-oxadiazole-2(3H)-thione | PDB:4Y83 | ||||
| Method | X-ray diffraction | Resolution | 2.89 Å | Mutation | No | [1] |
| PDB Sequence |
LSSVRYGTVE
82 DLLAFANHRP103 QESGILLNMV113 ITPQNGRYQI123 DSDVLLIPWK133 LTYRNIGSDF 143 IPRGAFGKVY153 LAQDIKTKKR163 MACKLIPVDQ173 FKPSDVEIQA183 CFRHENIAEL 193 YGAVLWGETV203 HLFMEAGEGG213 SVLEKLESCG223 PMREFEIIWV233 TKHVLKGLDF 243 LHSKKVIHHD253 IKPSNIVFMS263 TKAVLVDFGL273 SVQMTEDVYF283 PKDLRGTEIY 293 MSPEVILCRG303 HSTKADIYSL313 GATLIHMQTG323 TPPWVKRYYL340 YIIHKQAPPL 350 EDIADDCSPG360 MRELIEASLE370 RNPNHRPRAA380 DLLKHEALN
|
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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 .49B or .49B2 or .49B3 or :349B;style chemicals stick;color identity;select .A:132 or .A:133 or .A:134 or .A:144 or .A:146 or .A:152 or .A:165 or .A:167 or .A:191 or .A:207 or .A:208 or .A:209 or .A:210 or .A:213 or .A:214 or .A:217 or .A:257 or .A:258 or .A:260 or .A:269 or .A:270; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP132
3.581
LYS133
4.118
LEU134
3.820
ILE144
3.571
ARG146
3.405
VAL152
3.421
ALA165
3.598
LYS167
3.203
ALA191
4.481
MET207
3.481
GLU208
2.808
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold. J Biol Chem. 2015 Jun 12;290(24):15210-8. | ||||
| REF 2 | Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors. J Med Chem. 2016 Aug 25;59(16):7544-60. | ||||
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