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 | Cyclohexaneacetic acid, 4-[4-[6-(aminocarbonyl)-3,5-dimethyl-2-pyrazinyl]phenyl]-, trans- | Ligand Info | |||
| Canonical SMILES | O[P+](=O)O | ||||
| InChI | 1S/HO3P/c1-4(2)3/h(H-,1,2,3)/p+1 | ||||
| InChIKey | XNQULTQRGBXLIA-UHFFFAOYSA-O | ||||
| PubChem Compound ID | 3084169 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5AK0 Human PFKFB3 in complex with an indole inhibitor 6 | ||||||
| Method | X-ray diffraction | Resolution | 2.03 Å | Mutation | No | [1] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCGPNS33 PTVIVMVGLP43 ARGKTYISKK53 LTRYLNWIGV 63 PTKVFNVGEY73 RREAVKQYSS83 YNFFRPDNEE93 AMKVRKQCAL103 AALRDVKSYL 113 AKEGGQIAVF123 DATNTTRERR133 HMILHFAKEN143 DFKAFFIESV153 CDDPTVVASN 163 IMEVKISSPD173 YKDCNSAEAM183 DDFMKRISCY193 EASYQPLDPD203 KCDRDLSLIK 213 VIDVGRRFLV223 NRVQDHIQSR233 IVYYLMNIHV243 QPRTIYLCRH253 GENEHNLQGR 263 IGGDSGLSSR273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP 313 YEQWKALNEI323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ 363 DLVQRLEPVI373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL 413 HTVLKLTPVA423 YGCRVESIYL433 NVESVCTHRE443 RS
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| PDB ID: 5AJZ Human PFKFB3 in complex with an indole inhibitor 5 | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [1] |
| PDB Sequence |
LELTQSRVQK
11 IWVPVDHRPS21 LPRSCGNSPT35 VIVMVGLPAR45 GKTYISKKLT55 RYLNWIGVPT 65 KVFNVGEYRR75 EAVKQYSSYN85 FFRPDNEEAM95 KVRKQCALAA105 LRDVKSYLAK 115 EGGQIAVFDA125 TNTTRERRHM135 ILHFAKENDF145 KAFFIESVCD155 DPTVVASNIM 165 EVKISSPDYK175 DCNSAEAMDD185 FMKRISCYEA195 SYQPLDPDKC205 DRDLSLIKVI 215 DVGRRFLVNR225 VQDHIQSRIV235 YYLMNIHVQP245 RTIYLCRHGE255 NEHNLQGRIG 265 GDSGLSSRGK275 KFASALSKFV285 EEQNLKDLRV295 WTSQLKSTIQ305 TAEALRLPYE 315 QWKALNEIDA325 GVCEELTYEE335 IRDTYPEEYA345 LREQDKYYYR355 YPTGESYQDL 365 VQRLEPVIME375 LERQENVLVI385 CHQAVLRCLL395 AYFLDKSAEE405 MPYLKCPLHT 415 VLKLTPVAYG425 CRVESIYLNV435 ESVCTHRERS445
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| PDB ID: 5AJY Human PFKFB3 in complex with an indole inhibitor 4 | ||||||
| Method | X-ray diffraction | Resolution | 2.37 Å | Mutation | No | [1] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCNSPT35 VIVMVGLPAR45 GKTYISKKLT55 RYLNWIGVPT 65 KVFNVGEYRR75 EAVKQYSSYN85 FFRPDNEEAM95 KVRKQCALAA105 LRDVKSYLAK 115 EGGQIAVFDA125 TNTTRERRHM135 ILHFAKENDF145 KAFFIESVCD155 DPTVVASNIM 165 EVKISSPDYK175 DCNSAEAMDD185 FMKRISCYEA195 SYQPLDPDKC205 DRDLSLIKVI 215 DVGRRFLVNR225 VQDHIQSRIV235 YYLMNIHVQP245 RTIYLCRHGE255 NEHNLQGRIG 265 GDSGLSSRGK275 KFASALSKFV285 EEQNLKDLRV295 WTSQLKSTIQ305 TAEALRLPYE 315 QWKALNEIDA325 GVCEELTYEE335 IRDTYPEEYA345 LREQDKYYYR355 YPTGESYQDL 365 VQRLEPVIME375 LERQENVLVI385 CHQAVLRCLL395 AYFLDKSAEE405 MPYLKCPLHT 415 VLKLTPVAYG425 CRVESIYLNV435 ESVCTHRER
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| PDB ID: 2I1V Crystal structure of PFKFB3 in complex with ADP and Fructose-2,6-bisphosphate | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
LELTQSRVQK
11 IWVPVDHRPS21 LPRSCGPNSP34 TVIVMVGLPA44 RGKTYISKKL54 TRYLNWIGVP 64 TKVFNVGEYR74 REAVKQYSSY84 NFFRPDNEEA94 MKVRKQCALA104 ALRDVKSYLA 114 KEGGQIAVFD124 ATNTTRERRH134 MILHFAKEND144 FKAFFIESVC154 DDPTVVASNI 164 MEVKISSPDY174 KDCNSAEAMD184 DFMKRISCYE194 ASYQPLDPDK204 CDRDLSLIKV 214 IDVGRRFLVN224 RVQDHIQSRI234 VYYLMNIHVQ244 PRTIYLCRHG254 ENEHNLQGRI 264 GGDSGLSSRG274 KKFASALSKF284 VEEQNLKDLR294 VWTSQLKSTI304 QTAEALRLPY 314 EQWKALNEID324 AGVCEELTYE334 EIRDTYPEEY344 ALREQDKYYY354 RYPTGESYQD 364 LVQRLEPVIM374 ELERQENVLV384 ICHQAVLRCL394 LAYFLDKSAE404 EMPYLKCPLH 414 TVLKLTPVAY424 GCRVESIYLN434 VESVCTHRER444 SNPLMRRNS
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .B:252 or .B:253 or .B:256 or .B:259 or .B:322 or .B:386 or .B:387 or .B:388 or .B:413; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3QPV PFKFB3 trapped in a phospho-enzyme intermediate state | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVDHRPNS33 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 RSENPLMRRN459
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5AJW Human PFKFB3 in complex with an indole inhibitor 2 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [1] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSNSPTV36 IVMVGLPARG46 KTYISKKLTR56 YLNWIGVPTK 66 VFNVGEYRRE76 AVKQYSSYNF86 FRPDNEEAMK96 VRKQCALAAL106 RDVKSYLAKE 116 GGQIAVFDAT126 NTTRERRHMI136 LHFAKENDFK146 AFFIESVCDD156 PTVVASNIME 166 VKISSPDYKD176 CNSAEAMDDF186 MKRISCYEAS196 YQPLDPDKCD206 RDLSLIKVID 216 VGRRFLVNRV226 QDHIQSRIVY236 YLMNIHVQPR246 TIYLCRHGEN256 EHNLQGRIGG 266 DSGLSSRGKK276 FASALSKFVE286 EQNLKDLRVW296 TSQLKSTIQT306 AEALRLPYEQ 316 WKALNEIDAG326 VCEELTYEEI336 RDTYPEEYAL346 REQDKYYYRY356 PTGESYQDLV 366 QRLEPVIMEL376 ERQENVLVIC386 HQAVLRCLLA396 YFLDKSAEEM406 PYLKCPLHTV 416 LKLTPVAYGC426 RVESIYLNVE436 SVCTHRERS
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5AJX Human PFKFB3 in complex with an indole inhibitor 3 | ||||||
| Method | X-ray diffraction | Resolution | 2.58 Å | Mutation | No | [1] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCGPNS33 PTVIVMVGLP43 ARGKTYISKK53 LTRYLNWIGV 63 PTKVFNVGEY73 RREAVKQYSS83 YNFFRPDNEE93 AMKVRKQCAL103 AALRDVKSYL 113 AKEGGQIAVF123 DATNTTRERR133 HMILHFAKEN143 DFKAFFIESV153 CDDPTVVASN 163 IMEVKISSPD173 YKDCNSAEAM183 DDFMKRISCY193 EASYQPLDPD203 KCDRDLSLIK 213 VIDVGRRFLV223 NRVQDHIQSR233 IVYYLMNIHV243 QPRTIYLCRH253 GENEHNLQGR 263 IGGDSGLSSR273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP 313 YEQWKALNEI323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ 363 DLVQRLEPVI373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL 413 HTVLKLTPVA423 YGCRVESIYL433 NVESVCTHRE443 R
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4D4M human PFKFB3 in complex with a pyrrolopyrimidone compound | ||||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | No | [4] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCNSPT35 VIVMVGLPAR45 GKTYISKKLT55 RYLNWIGVPT 65 KVFNVGEYRR75 EAVKQYSSYN85 FFRPDNEEAM95 KVRKQCALAA105 LRDVKSYLAK 115 EGGQIAVFDA125 TNTTRERRHM135 ILHFAKENDF145 KAFFIESVCD155 DPTVVASNIM 165 EVKISSPDYK175 DCNSAEAMDD185 FMKRISCYEA195 SYQPLDPDKC205 DRDLSLIKVI 215 DVGRRFLVNR225 VQDHIQSRIV235 YYLMNIHVQP245 RTIYLCRHGE255 NEHNLQGRIG 265 GDSGLSSRGK275 KFASALSKFV285 EEQNLKDLRV295 WTSQLKSTIQ305 TAEALRLPYE 315 QWKALNEIDA325 GVCEELTYEE335 IRDTYPEEYA345 LREQDKYYYR355 YPTGESYQDL 365 VQRLEPVIME375 LERQENVLVI385 CHQAVLRCLL395 AYFLDKSAEE405 MPYLKCPLHT 415 VLKLTPVAYG425 CRVESIYLNV435 ESVCTHRER
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4D4J human PFKFB3 in complex with a pyrrolopyrimidone compound | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [5] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCGPNS33 PTVIVMVGLP43 ARGKTYISKK53 LTRYLNWIGV 63 PTKVFNVGEY73 RREAVKQYSS83 YNFFRPDNEE93 AMKVRKQCAL103 AALRDVKSYL 113 AKEGGQIAVF123 DATNTTRERR133 HMILHFAKEN143 DFKAFFIESV153 CDDPTVVASN 163 IMEVKISSPD173 YKDCNSAEAM183 DDFMKRISCY193 EASYQPLDPD203 KCDRDLSLIK 213 VIDVGRRFLV223 NRVQDHIQSR233 IVYYLMNIHV243 QPRTIYLCRH253 GENEHNLQGR 263 IGGDSGLSSR273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP 313 YEQWKALNEI323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ 363 DLVQRLEPVI373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL 413 HTVLKLTPVA423 YGCRVESIYL433 NVESVCTHRE443 RS
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:387 or .A:388; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4D4L human PFKFB3 in complex with a pyrrolopyrimidone compound | ||||||
| Method | X-ray diffraction | Resolution | 3.16 Å | Mutation | No | [6] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSCGPNS33 PTVIVMVGLP43 ARGKTYISKK53 LTRYLNWIGV 63 PTKVFNVGEY73 RREAVKQYSS83 YNFFRPDNEE93 AMKVRKQCAL103 AALRDVKSYL 113 AKEGGQIAVF123 DATNTTRERR133 HMILHFAKEN143 DFKAFFIESV153 CDDPTVVASN 163 IMEVKISSPD173 YKDCNSAEAM183 DDFMKRISCY193 EASYQPLDPD203 KCDRDLSLIK 213 VIDVGRRFLV223 NRVQDHIQSR233 IVYYLMNIHV243 QPRTIYLCRH253 GENEHNLQGR 263 IGGDSGLSSR273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP 313 YEQWKALNEI323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ 363 DLVQRLEPVI373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL 413 HTVLKLTPVA423 YGCRVESIYL433 NVESVCTHRE443 RS
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4D4K human PFKFB3 in complex with a pyrrolopyrimidone compound | ||||||
| Method | X-ray diffraction | Resolution | 3.24 Å | Mutation | No | [7] |
| PDB Sequence |
PLELTQSRVQ
10 KIWVPVDHRP20 SLPRSNSPTV36 IVMVGLPARG46 KTYISKKLTR56 YLNWIGVPTK 66 VFNVGEYRRE76 AVKQYSSYNF86 FRPDNEEAMK96 VRKQCALAAL106 RDVKSYLAKE 116 GGQIAVFDAT126 NTTRERRHMI136 LHFAKENDFK146 AFFIESVCDD156 PTVVASNIME 166 VKISSPDYKD176 CNSAEAMDDF186 MKRISCYEAS196 YQPLDPDKCD206 RDLSLIKVID 216 VGRRFLVNRV226 QDHIQSRIVY236 YLMNIHVQPR246 TIYLCRHGEN256 EHNLQGRIGG 266 DSGLSSRGKK276 FASALSKFVE286 EQNLKDLRVW296 TSQLKSTIQT306 AEALRLPYEQ 316 WKALNEIDAG326 VCEELTYEEI336 RDTYPEEYAL346 REQDKYYYRY356 PTGESYQDLV 366 QRLEPVIMEL376 ERQENVLVIC386 HQAVLRCLLA396 YFLDKSAEEM406 PYLKCPLHTV 416 LKLTPVAYGC426 RVESIYLNVE436 SVCTHRERS
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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 .PHS or .PHS2 or .PHS3 or :3PHS;style chemicals stick;color identity;select .A:252 or .A:253 or .A:256 or .A:259 or .A:322 or .A:386 or .A:387 or .A:388 or .A:413; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3. J Med Chem. 2015 Apr 23;58(8):3611-25. | ||||
| REF 2 | A direct substrate-substrate interaction found in the kinase domain of the bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. J Mol Biol. 2007 Jun 29;370(1):14-26. | ||||
| REF 3 | 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 4 | Identifying a Novel Series of Pfkfb3 Inhibitors as a Metabolic Approach to Treating Cancer from Hts, Biophysical and Biochemical Methods | ||||
| REF 5 | Identifying a Novel Series of Pfkfb3 Inhibitors as a Metabolic Approach to Treating Cancer from Hts, Biophysical and Biochemical Methods | ||||
| REF 6 | Identifying a Novel Series of Pfkfb3 Inhibitors as a Metabolic Approach to Treating Cancer from Hts, Biophysical and Biochemical Methods | ||||
| REF 7 | Identifying a Novel Series of Pfkfb3 Inhibitors as a Metabolic Approach to Treating Cancer from Hts, Biophysical and Biochemical Methods | ||||
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