Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T94479 | Target Info | |||
| Target Name | Ribosomal protein S6 kinase beta-1 (S6K1) | ||||
| Synonyms | p70-S6K 1; p70 ribosomal S6 kinase alpha; p70 S6KA; p70 S6K-alpha; p70 S6 kinase alpha; Serine/threonine-protein kinase 14A; STK14A; S6K-beta-1; S6K; Ribosomal protein S6 kinase I; P70S6K1; P70-S6K; 70 kDa ribosomal protein S6 kinase 1 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | RPS6KB1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Phosphonothreonine | Ligand Info | |||
| Canonical SMILES | CC(C(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C4H10NO6P/c1-2(3(5)4(6)7)11-12(8,9)10/h2-3H,5H2,1H3,(H,6,7)(H2,8,9,10)/t2-,3+/m1/s1 | ||||
| InChIKey | USRGIUJOYOXOQJ-GBXIJSLDSA-N | ||||
| PubChem Compound ID | 3246323 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4L46 Crystal structures of human p70S6K1-WT | ||||||
| Method | X-ray diffraction | Resolution | 3.01 Å | Mutation | No | [1] |
| PDB Sequence |
NRGPEKIRPE
66 CFELLRVLGK76 GGYGKVFQVR86 KVTGANTGKI96 FAMKVLKKAM106 IVRNAKDTAH 116 TKAERNILEE126 VKHPFIVDLI136 YAFQTGGKLY146 LILEYLSGGE156 LFMQLEREGI 166 FMEDTACFYL176 AEISMALGHL186 HQKGIIYRDL196 KPENIMLNHQ206 GHVKLTDFGL 216 CKESIHDHTF230 CGTIEYMAPE240 ILMRSGHNRA250 VDWWSLGALM260 YDMLTGAPPF 270 TGENRKKTID280 KILKCKLNLP290 PYLTQEARDL300 LKKLLKRNAA310 SRLGAGPGDA 320 GEVQAHPFFR330 HINWEELLAR340 KVEPPFKPLE353 EDVSQFDSKF363 TRQTPVQVFL 386 GFYVAPS
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| PDB ID: 7N93 P70 S6K1 IN COMPLEX WITH MSC2363318A-1 | ||||||
| Method | X-ray diffraction | Resolution | 2.74 Å | Mutation | Yes | [2] |
| PDB Sequence |
RPECFELLRV
96 LGKGGYGKVF106 QVRKVTGANT116 GKIFAMKVLK126 KAMIVRNAKD136 TAHTKAERNI 146 LEEVKHPFIV156 DLIYAFQTGG166 KLYLILEYLS176 GGELFMQLER186 EGIFMEDTAC 196 FYLAEISMAL206 GHLHQKGIIY216 RDLKPENIML226 NHQGHVKLTD236 FGLCKECGTI 257 EYMAPEILMR267 SGHNRAVDWW277 SLGALMYDML287 TGAPPFTGEN297 RKKTIDKILK 307 CKLNLPPYLT317 QEARDLLKKL327 LKRNAASRLG337 AGPGDAGEVQ347 AHPFFRHINW 357 EELLARKVEP367 PFKPLLQSEE377 DVSQFDSKFT387 RQPVDPNQVF408 LGFEYVAPSV 418
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| PDB ID: 7N91 P70 S6K1 IN COMPLEX WITH MSC2317067A-1 | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVNTG117 KIFAMKVLKK127 AMIVRNAKDT137 AHTKAERNIL 147 EEVKHPFIVD157 LIYAFQTGGK167 LYLILEYLSG177 GELFMQLERE187 GIFMEDTACF 197 YLAEISMALG207 HLHQKGIIYR217 DLKPENIMLN227 HQGHVKLTDF237 GLGTIEYMAP 262 EILMRSGHNR272 AVDWWSLGAL282 MYDMLTGAPP292 FTGENRKKTI302 DKILKCKLNL 312 PPYLTQEARD322 LLKKLLKRNA332 ASRLGAGPGD342 AGEVQAHPFF352 RHINWEELLA 362 RKVEPPFKPL372 LQSEEDVSQF382 DSKFTRQPVD393 PNQVFLGFEY413 VAPSV |
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| PDB ID: 3WF7 Crystal structure of S6K1 kinase domain in complex with a purine derivative 1-(9H-purin-6-yl)-N-[3-(trifluoromethyl)phenyl]piperidine-4-carboxamide | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [3] |
| PDB Sequence |
PEKIRPECFE
92 LLRVLGKGGY102 GKVFQVRKVT112 GANTGKIFAM122 KVLKKAMIVR132 NAKDTAHTKA 142 ERNILEEVKH152 PFIVDLIYAF162 QTGGKLYLIL172 EYLSGGELFM182 QLEREGIFME 192 DTACFYLAEI202 SMALGHLHQK212 GIIYRDLKPE222 NIMLNHQGHV232 KLTDFGLCKE 242 SIHDTHFCGT256 IEYMAPEILM266 RSGHNRAVDW276 WSLGALMYDM286 LTGAPPFTGE 296 NRKKTIDKIL306 KCKLNLPPYL316 TQEARDLLKK326 LLKRNAASRL336 GAGPGDAGEV 346 QAHPFFRHIN356 WEELLARKVE366 PPFKPLLQ
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:217 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:260 or .A:264 or .A:265 or .A:267; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3WF8 Crystal structure of S6K1 kinase domain in complex with a quinoline derivative 2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl 7,8,9,10-tetrahydro-6H-cyclohepta[b]quinoline-11-carboxylate | ||||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [3] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKAMIVRNA134 KDTAHTKAER 144 NILEEVKHPF154 IVDLIYAFQT164 GGKLYLILEY174 LSGGELFMQL184 EREGIFMEDT 194 ACFYLAEISM204 ALGHLHQKGI214 IYRDLKPENI224 MLNHQGHVKL234 TDFGLCKESI 244 HDGTVTHFCG255 TIEYMAPEIL265 MRSGHNRAVD275 WWSLGALMYD285 MLTGAPPFTG 295 ENRKKTIDKI305 LKCKLNLPPY315 LTQEARDLLK325 KLLKRNAASR335 LGAGPGDAGE 345 VQAHPFFRHI355 NWEELLARKV365 EPPFKPL
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:135 or .A:217 or .A:218 or .A:250 or .A:251 or .A:253 or .A:254 or .A:260 or .A:264 or .A:267; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3WE4 Crystal structure of S6K1 kinase domain in complex with a pyrimidine derivative PF-4708671 2-{[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl}-5-(trifluoromethyl)-1H-benzimidazole | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKAMIVRNA134 KDTAHTKAER 144 NILEEVKHPF154 IVDLIYAFQT164 GGKLYLILEY174 LSGGELFMQL184 EREGIFMEDT 194 ACFYLAEISM204 ALGHLHQKGI214 IYRDLKPENI224 MLNHQGHVKL234 TDFGLCKESI 244 HDTHFCGTIE258 YMAPEILMRS268 GHNRAVDWWS278 LGALMYDMLT288 GAPPFTGENR 298 KKTIDKILKC308 KLNLPPYLTQ318 EARDLLKKLL328 KRNAASRLGA338 GPGDAGEVQA 348 HPFFRHINWE358 ELLARKVEPP368 FKPLLQ
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:217 or .A:250 or .A:251 or .A:253 or .A:254 or .A:255 or .A:257 or .A:260 or .A:264 or .A:265 or .A:267; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3WF6 Crystal structure of S6K1 kinase domain in complex with a pyrazolopyrimidine derivative 4-[4-(1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl]-1H-pyrazolo[3,4-d]pyrimidine | ||||||
| Method | X-ray diffraction | Resolution | 2.03 Å | Mutation | No | [3] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKTKAERNI146 LEEVKHPFIV 156 DLIYAFQTGG166 KLYLILEYLS176 GGELFMQLER186 EGIFMEDTAC196 FYLAEISMAL 206 GHLHQKGIIY216 RDLKPENIML226 NHQGHVKLTD236 FGLCKESIHD246 GTVTHFCGTI 257 EYMAPEILMR267 SGHNRAVDWW277 SLGALMYDML287 TGAPPFTGEN297 RKKTIDKILK 307 CKLNLPPYLT317 QEARDLLKKL327 LKRNAASRLG337 AGPGDAGEVQ347 AHPFFRHINW 357 EELLARKVEP367 PFKPLLQ
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:217 or .A:250 or .A:251 or .A:253 or .A:254 or .A:255 or .A:257 or .A:260 or .A:264 or .A:265 or .A:267; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3WF9 Crystal structure of S6K1 kinase domain in complex with a quinoline derivative 1-oxo-1-[(4-sulfamoylphenyl)amino]propan-2-yl-2-methyl-1,2,3,4-tetrahydroacridine-9-carboxylate | ||||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [3] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKAMIVRNA134 KDTAHTKAER 144 NILEEVKHPF154 IVDLIYAFQT164 GGKLYLILEY174 LSGGELFMQL184 EREGIFMEDT 194 ACFYLAEISM204 ALGHLHQKGI214 IYRDLKPENI224 MLNHQGHVKL234 TDFGLCKESI 244 HDGTVTHFCG255 TIEYMAPEIL265 MRSGHNRAVD275 WWSLGALMYD285 MLTGAPPFTG 295 ENRKKTIDKI305 LKCKLNLPPY315 LTQEARDLLK325 KLLKRNAASR335 LGAGPGDAGE 345 VQAHPFFRHI355 NWEELLARKV365 EPPFKPL
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:135 or .A:217 or .A:218 or .A:250 or .A:251 or .A:253 or .A:254 or .A:260 or .A:264 or .A:267; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3WF5 Crystal structure of S6K1 kinase domain in complex with a pyrazolopyrimidine derivative 4-[4-(1H-benzimidazol-2-yl)piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKTKAERNI146 LEEVKHPFIV 156 DLIYAFQTGG166 KLYLILEYLS176 GGELFMQLER186 EGIFMEDTAC196 FYLAEISMAL 206 GHLHQKGIIY216 RDLKPENIML226 NHQGHVKLTD236 FGLCKESIHD246 GTVTHFCGTI 257 EYMAPEILMR267 SGHNRAVDWW277 SLGALMYDML287 TGAPPFTGEN297 RKKTIDKILK 307 CKLNLPPYLT317 QEARDLLKKL327 LKRNAASRLG337 AGPGDAGEVQ347 AHPFFRHINW 357 EELLARKVEP367 PFKPLLQ
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:217 or .A:250 or .A:251 or .A:253 or .A:254 or .A:255 or .A:257 or .A:260 or .A:264 or .A:265 or .A:267; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3A62 Crystal structure of phosphorylated p70S6K1 | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [4] |
| PDB Sequence |
KIRPECFELL
94 RVLGKGGYGK104 VFQVRKVTGA114 NTGKIFAMKV124 LKKAERNILE148 EVKHPFIVDL 158 IYAFQTGGKL168 YLILEYLSGG178 ELFMQLEREG188 IFMEDTACFY198 LAEISMALGH 208 LHQKGIIYRD218 LKPENIMLNH228 QGHVKLTDFG238 LCHFCGTIEY259 MAPEILMRSG 269 HNRAVDWWSL279 GALMYDMLTG289 APPFTGENRK299 KTIDKILKCK309 LNLPPYLTQE 319 ARDLLKKLLK329 RNAASRLGAG339 PGDAGEVQAH349 PFFRHINWEE359 LLARKVEPPF 369 KPL
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:217 or .A:251 or .A:253 or .A:254 or .A:255 or .A:257 or .A:260 or .A:264 or .A:265 or .A:267 or .A:298; 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 | Crystal structures of S6K1 provide insights into the regulation mechanism of S6K1 by the hydrophobic motif. Biochem J. 2013 Aug 15;454(1):39-47. | ||||
| REF 2 | Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers. J Med Chem. 2021 Oct 14;64(19):14603-14619. | ||||
| REF 3 | Crystal structures of the S6K1 kinase domain in complexes with inhibitors. J Struct Funct Genomics. 2014 Sep;15(3):153-64. | ||||
| REF 4 | Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. J Biol Chem. 2010 Feb 12;285(7):4587-94. | ||||
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