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 | adenosine diphosphate | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)O)O)O)N | ||||
| InChI | 1S/C10H15N5O10P2/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(24-10)1-23-27(21,22)25-26(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | XTWYTFMLZFPYCI-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 6022 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 2AXN Crystal structure of the human inducible form 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| 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 SNPLMRRNSS731 S |
|||||
|
|
LEU42
3.690
PRO43
3.653
ALA44
2.798
ARG45
2.900
GLY46
3.043
LYS47
2.749
THR48
2.721
TYR49
2.733
ILE50
4.281
ASP124
4.508
SER152
3.493
CYS154
4.113
VAL159
3.883
|
|||||
| PDB ID: 4MA4 S-glutathionylated PFKFB3 | ||||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | No | [2] |
| PDB Sequence |
LELTQSRVQK
11 IWVPVDHRPS21 LPNSPTVIVM39 VGLPARGKTY49 ISKKLTRYLN59 WIGVPTKVFN 69 VGEYRREAVK79 QYSSYNFFRP89 DNEEAMKVRK99 QCALAALRDV109 KSYLAKEGGQ 119 IAVFDATNTT129 RERRHMILHF139 AKENDFKAFF149 IESVCDDPTV159 VASNIMEVKI 169 SSPDYKDCNS179 AEAMDDFMKR189 ISCYEASYQP199 LDPDKCDRDL209 SLIKVIDVGR 219 RFLVNRVQDH229 IQSRIVYYLM239 NIHVQPRTIY249 LCRHGENEHN259 LQGRIGGDSG 269 LSSRGKKFAS279 ALSKFVEEQN289 LKDLRVWTSQ299 LKSTIQTAEA309 LRLPYEQWKA 319 LNEIDAGVCE329 ELTYEEIRDT339 YPEEYALREQ349 DKYYYRYPTG359 ESYQDLVQRL 369 EPVIMELERQ379 ENVLVICHQA389 VLRCLLAYFL399 DKSAEEMPYL409 KCPLHTVLKL 419 TPVAYGCRVE429 SIYLNVESVC439 THRERSNPLM456 RRNS
|
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|
|
LEU42
3.846
PRO43
3.734
ALA44
2.777
ARG45
3.043
GLY46
3.084
LYS47
2.808
THR48
2.804
TYR49
2.752
ILE50
4.211
ASP124
4.369
SER152
3.499
CYS154
4.264
|
|||||
| PDB ID: 2DWO PFKFB3 in complex with ADP and PEP | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [3] |
| 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
|
|||||
|
|
LEU42
3.811
PRO43
3.637
ALA44
2.766
ARG45
2.847
GLY46
2.950
LYS47
2.832
THR48
2.987
TYR49
2.764
ILE50
4.126
ASP124
4.802
SER152
3.436
CYS154
4.190
|
|||||
| PDB ID: 3QPW PFKFB3 in complex with Aluminum Tetrafluoride | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [4] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVDHRPSL22 PRSNSPTVIV38 MVGLPARGKT48 YISKKLTRYL58 NWIGVPTKVF 68 NVGEYRREAV78 KQYSSYNFFR88 PDNEEAMKVR98 KQCALAALRD108 VKSYLAKEGG 118 QIAVFDATNT128 TRERRHMILH138 FAKENDFKAF148 FIESVCDDPT158 VVASNIMEVK 168 ISSPDYKDCN178 SAEAMDDFMK188 RISCYEASYQ198 PLDPDKCDRD208 LSLIKVIDVG 218 RRFLVNRVQD228 HIQSRIVYYL238 MNIHVQPRTI248 YLCRHGENEH258 NLQGRIGGDS 268 GLSSRGKKFA278 SALSKFVEEQ288 NLKDLRVWTS298 QLKSTIQTAE308 ALRLPYEQWK 318 ALNEIDAGVC328 EELTYEEIRD338 TYPEEYALRE348 QDKYYYRYPT358 GESYQDLVQR 368 LEPVIMELER378 QENVLVICHQ388 AVLRCLLAYF398 LDKSAEEMPY408 LKCPLHTVLK 418 LTPVAYGCRV428 ESIYLNVESV438 C
|
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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 .ADP or .ADP2 or .ADP3 or :3ADP;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:50 or .A:124 or .A:152 or .A:154 or .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:168 or .A:186 or .A:214 or .A:217 or .A:218 or .A:243 or .A:423 or .A:424; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU42
3.697
PRO43
3.697
ALA44
2.723
ARG45
3.015
GLY46
3.125
LYS47
2.829
THR48
2.937
TYR49
2.785
ILE50
4.249
ASP124
4.491
SER152
3.500
CYS154
4.063
VAL159
3.886
|
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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 | [3] |
| 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 .ADP or .ADP2 or .ADP3 or :3ADP;style chemicals stick;color identity;select .B:42 or .B:43 or .B:44 or .B:45 or .B:46 or .B:47 or .B:48 or .B:49 or .B:50 or .B:124 or .B:152 or .B:154 or .B:159 or .B:163 or .B:166 or .B:167 or .B:168 or .B:186 or .B:214 or .B:217 or .B:218 or .B:243 or .B:424; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU42
3.791
PRO43
3.389
ALA44
2.529
ARG45
2.726
GLY46
2.987
LYS47
2.829
THR48
2.962
TYR49
2.666
ILE50
4.146
ASP124
4.793
SER152
3.669
CYS154
4.266
|
|||||
| PDB ID: 3QPV PFKFB3 trapped in a phospho-enzyme intermediate state | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| 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 .ADP or .ADP2 or .ADP3 or :3ADP;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:50 or .A:124 or .A:152 or .A:154 or .A:159 or .A:163 or .A:166 or .A:167 or .A:168 or .A:186 or .A:214 or .A:217 or .A:218 or .A:243 or .A:423 or .A:424; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU42
3.740
PRO43
3.660
ALA44
2.656
ARG45
2.645
GLY46
3.093
LYS47
2.754
THR48
2.899
TYR49
2.845
ILE50
4.449
ASP124
4.840
SER152
3.524
CYS154
4.097
|
|||||
| PDB ID: 6ETJ HUMAN PFKFB3 IN COMPLEX WITH KAN0438241 | ||||||
| Method | X-ray diffraction | Resolution | 2.51 Å | Mutation | No | [5] |
| PDB Sequence |
ELTQSRVQKI
12 WVPVDHRPSL22 SPTVIVMVGL42 PARGKTYISK52 KLTRYLNWIG62 VPTKVFNVGE 72 YRREAVKQYS82 SYNFFRPDNE92 EAMKVRKQCA102 LAALRDVKSY112 LAKEGGQIAV 122 FDATNTTRER132 RHMILHFAKE142 NDFKAFFIES152 VCDDPTVVAS162 NIMEVKISSP 172 DYKDCNSAEA182 MDDFMKRISC192 YEASYQPLDP202 DKCDRDLSLI212 KVIDVGRRFL 222 VNRVQDHIQS232 RIVYYLMNIH242 VQPRTIYLCR252 GENEHNLQGR263 IGGDSGLSSR 273 GKKFASALSK283 FVEEQNLKDL293 RVWTSQLKST303 IQTAEALRLP313 YEQWKALNEI 323 DAGVCEELTY333 EEIRDTYPEE343 YALREQDKYY353 YRYPTGESYQ363 DLVQRLEPVI 373 MELERQENVL383 VICHQAVLRC393 LLAYFLDKSA403 EEMPYLKCPL413 HTVLKLTPVA 423 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 .ADP or .ADP2 or .ADP3 or :3ADP;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:50 or .A:124 or .A:152 or .A:154 or .A:159 or .A:163 or .A:166 or .A:167 or .A:168 or .A:214 or .A:217 or .A:218 or .A:243 or .A:423 or .A:424; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU42
3.765
PRO43
3.783
ALA44
2.865
ARG45
2.932
GLY46
2.847
LYS47
2.694
THR48
2.878
TYR49
2.728
ILE50
4.669
ASP124
4.637
SER152
3.902
CYS154
4.190
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3): a possible new target for cancer therapy. J Biol Chem. 2006 Feb 3;281(5):2939-44. | ||||
| REF 2 | PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer. J Mol Biol. 2014 Feb 20;426(4):830-42. | ||||
| REF 3 | 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 4 | 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 5 | Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nat Commun. 2018 Sep 24;9(1):3872. | ||||
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