Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T23787 | Target Info | |||
| Target Name | Renal carcinoma antigen NY-REN-56 (PFKFB3) | ||||
| Synonyms | iPFK2; Renal carcinoma antigen NYREN56; PFKFB3; Fructose2,6bisphosphatase; 6phosphofructo2kinase/fructose2,6bisphosphatase 3; 6PF2K/Fru2,6P2ase brain/placentatype isozyme; 6PF2K/Fru2,6P2ase 3 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PFKFB3 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Pyrophosphate 2- | Ligand Info | |||
| Canonical SMILES | OP(=O)([O-])OP(=O)(O)[O-] | ||||
| InChI | 1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)/p-2 | ||||
| InChIKey | XPPKVPWEQAFLFU-UHFFFAOYSA-L | ||||
| PubChem Compound ID | 4995 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6HVI Human PFKFB3 in complex with a N-Aryl 6-Aminoquinoxaline inhibitor 2 | ||||||
| Method | X-ray diffraction | Resolution | 1.96 Å | Mutation | No | [1] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVHRNS33 PTVIVMVGLP43 ARGKTYISKK53 LTRYLNWIGV63 PTKVFNVGEY 73 RREAVKQYSS83 YNFFRPDNEE93 AMKVRKQCAL103 AALRDVKSYL113 AKEGGQIAVF 123 DATNTTRERR133 HMILHFAKEN143 DFKAFFIESV153 CDDPTVVASN163 IMEVKISSPD 173 YKDCNSAEAM183 DDFMKRISCY193 EASYQPLDPD203 KCDRDLSLIK213 VIDVGRRFLV 223 NRVQDHIQSR233 IVYYLMNIHV243 QPRTIYLCRH253 GENEHNLQGR263 IGGDSGLSSR 273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP313 YEQWKALNEI 323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ363 DLVQRLEPVI 373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL413 HTVLKLTPVA 423 YGCRVESIYL433 NVESVCTHRE443 RSE
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| PDB ID: 3QPU PFKFB3 in complex with PPi | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVDHRPSL22 PRSCGSPTVI37 VMVGLPARGK47 TYISKKLTRY57 LNWIGVPTKV 67 FNVGEYRREA77 VKQYSSYNFF87 RPDNEEAMKV97 RKQCALAALR107 DVKSYLAKEG 117 GQIAVFDATN127 TTRERRHMIL137 HFAKENDFKA147 FFIESVCDDP157 TVVASNIMEV 167 KISSPDYKDC177 NSAEAMDDFM187 KRISCYEASY197 QPLDPDKCDR207 DLSLIKVIDV 217 GRRFLVNRVQ227 DHIQSRIVYY237 LMNIHVQPRT247 IYLCRHGENE257 HNLQGRIGGD 267 SGLSSRGKKF277 ASALSKFVEE287 QNLKDLRVWT297 SQLKSTIQTA307 EALRLPYEQW 317 KALNEIDAGV327 CEELTYEEIR337 DTYPEEYALR347 EQDKYYYRYP357 TGESYQDLVQ 367 RLEPVIMELE377 RQENVLVICH387 QAVLRCLLAY397 FLDKSAEEMP407 YLKCPLHTVL 417 KLTPVAYGCR427 VESIYLNVES437 VCTHRERSE
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LEU42
3.749
PRO43
3.688
ALA44
2.751
ARG45
3.102
GLY46
2.985
LYS47
2.673
THR48
2.768
TYR49
2.849
VAL70
3.754
GLY71
3.281
ARG74
2.812
PHE87
3.454
ARG98
2.915
ASP124
4.394
ALA125
3.548
THR126
2.634
ASN127
4.859
ASN163
4.019
VAL167
3.390
LYS168
2.845
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| PDB ID: 6HVH Human PFKFB3 in complex with a N-Aryl 6-Aminoquinoxaline inhibitor 1 | ||||||
| Method | X-ray diffraction | Resolution | 2.36 Å | Mutation | No | [1] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVDHNSPT35 VIVMVGLPAR45 GKTYISKKLT55 RYLNWIGVPT65 KVFNVGEYRR 75 EAVKQYSSYN85 FFRPDNEEAM95 KVRKQCALAA105 LRDVKSYLAK115 EGGQIAVFDA 125 TNTTRERRHM135 ILHFAKENDF145 KAFFIESVCD155 DPTVVASNIM165 EVKISSPDYK 175 DCNSAEAMDD185 FMKRISCYEA195 SYQPLDPDKC205 DRDLSLIKVI215 DVGRRFLVNR 225 VQDHIQSRIV235 YYLMNIHVQP245 RTIYLCRHGE255 NEHNLQGRIG265 GDSGLSSRGK 275 KFASALSKFV285 EEQNLKDLRV295 WTSQLKSTIQ305 TAEALRLPYE315 QWKALNEIDA 325 GVCEELTYEE335 IRDTYPEEYA345 LREQDKYYYR355 YPTGESYQDL365 VQRLEPVIME 375 LERQENVLVI385 CHQAVLRCLL395 AYFLDKSAEE405 MPYLKCPLHT415 VLKLTPVAYG 425 CRVESIYLNV435 ESVCTHRERS445 E
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| PDB ID: 6IBX Human PFKFB3 in complex with a N-Aryl 6-Aminoquinoxaline inhibitor 5 | ||||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [3] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVNSPTVI37 VMVGLPARGK47 TYISKKLTRY57 LNWIGVPTKV67 FNVGEYRREA 77 VKQYSSYNFF87 RPDNEEAMKV97 RKQCALAALR107 DVKSYLAKEG117 GQIAVFDATN 127 TTRERRHMIL137 HFAKENDFKA147 FFIESVCDDP157 TVVASNIMEV167 KISSPDYKDC 177 NSAEAMDDFM187 KRISCYEASY197 QPLDPDKCDR207 DLSLIKVIDV217 GRRFLVNRVQ 227 DHIQSRIVYY237 LMNIHVQPRT247 IYLCRHGENE257 HNLQGRIGGD267 SGLSSRGKKF 277 ASALSKFVEE287 QNLKDLRVWT297 SQLKSTIQTA307 EALRLPYEQW317 KALNEIDAGV 327 CEELTYEEIR337 DTYPEEYALR347 EQDKYYYRYP357 TGESYQDLVQ367 RLEPVIMELE 377 RQENVLVICH387 QAVLRCLLAY397 FLDKSAEEMP407 YLKCPLHTVL417 KLTPVAYGCR 427 VESIYLNVES437 VCTHRERSE
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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 .POP or .POP2 or .POP3 or :3POP;style chemicals stick;color identity;select .A:42 or .A:43 or .A:44 or .A:45 or .A:46 or .A:47 or .A:48 or .A:49 or .A:124 or .A:163 or .A:167 or .A:168 or .A:424; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 6IBY Human PFKFB3 in complex with a N-Aryl 6-Aminoquinoxaline inhibitor 6 | ||||||
| Method | X-ray diffraction | Resolution | 2.51 Å | Mutation | No | [3] |
| PDB Sequence |
ELTQSRVQKI
12 WVPNSPTVIV38 MVGLPARGKT48 YISKKLTRYL58 NWIGVPTKVF68 NVGEYRREAV 78 KQYSSYNFFR88 PDNEEAMKVR98 KQCALAALRD108 VKSYLAKEGG118 QIAVFDATNT 128 TRERRHMILH138 FAKENDFKAF148 FIESVCDDPT158 VVASNIMEVK168 ISSPDYKDCN 178 SAEAMDDFMK188 RISCYEASYQ198 PLDPDKCDRD208 LSLIKVIDVG218 RRFLVNRVQD 228 HIQSRIVYYL238 MNIHVQPRTI248 YLCRHGENEH258 NLQGRIGGDS268 GLSSRGKKFA 278 SALSKFVEEQ288 NLKDLRVWTS298 QLKSTIQTAE308 ALRLPYEQWK318 ALNEIDAGVC 328 EELTYEEIRD338 TYPEEYALRE348 QDKYYYRYPT358 GESYQDLVQR368 LEPVIMELER 378 QENVLVICHQ388 AVLRCLLAYF398 LDKSAEEMPY408 LKCPLHTVLK418 LTPVAYGCRV 428 ESIYLNVESV438 CTHRERSE
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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 .POP or .POP2 or .POP3 or :3POP;style chemicals stick;color identity;select .A:42 or .A:43 or .A:44 or .A:45 or .A:46 or .A:47 or .A:48 or .A:49 or .A:124 or .A:163 or .A:167 or .A:168 or .A:424; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 6IC0 Human PFKFB3 in complex with a N-Aryl 6-Aminoquinoxaline inhibitor 4 | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVNSPTVI37 VMVGLPARGK47 TYISKKLTRY57 LNWIGVPTKV67 FNVGEYRREA 77 VKQYSSYNFF87 RPDNEEAMKV97 RKQCALAALR107 DVKSYLAKEG117 GQIAVFDATN 127 TTRERRHMIL137 HFAKENDFKA147 FFIESVCDDP157 TVVASNIMEV167 KISSPDYKDC 177 NSAEAMDDFM187 KRISCYEASY197 QPLDPDKCDR207 DLSLIKVIDV217 GRRFLVNRVQ 227 DHIQSRIVYY237 LMNIHVQPRT247 IYLCRHGENE257 HNLQGRIGGD267 SGLSSRGKKF 277 ASALSKFVEE287 QNLKDLRVWT297 SQLKSTIQTA307 EALRLPYEQW317 KALNEIDAGV 327 CEELTYEEIR337 DTYPEEYALR347 EQDKYYYRYP357 TGESYQDLVQ367 RLEPVIMELE 377 RQENVLVICH387 QAVLRCLLAY397 FLDKSAEEMP407 YLKCPLHTVL417 KLTPVAYGCR 427 VESIYLNVES437 VCTHRERS
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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 .POP or .POP2 or .POP3 or :3POP;style chemicals stick;color identity;select .A:42 or .A:43 or .A:44 or .A:45 or .A:46 or .A:47 or .A:48 or .A:49 or .A:124 or .A:163 or .A:167 or .A:168 or .A:186 or .A:424; 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 | Discovery and Structure-Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors. ChemMedChem. 2019 Jan 8;14(1):169-181. | ||||
| REF 2 | Molecular basis of the fructose-2,6-bisphosphatase reaction of PFKFB3: transition state and the C-terminal function. Proteins. 2012 Apr;80(4):1143-53. | ||||
| REF 3 | Synthesis of amide and sulfonamide substituted N-aryl 6-aminoquinoxalines as PFKFB3 inhibitors with improved physicochemical properties. Bioorg Med Chem Lett. 2019 Feb 15;29(4):646-653. | ||||
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