Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T06958 | Target Info | |||
| Target Name | DNA polymerase beta (POLB) | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | POLB | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 2'-Deoxy-5'-O-[(R)-{[(R)-[(R)-Fluoro(Phosphono)methyl](Hydroxy)phosphoryl]oxy}(Hydroxy)phosphoryl]guanosine | Ligand Info | |||
| Canonical SMILES | C1C(C(OC1N2C=NC3=C2N=C(NC3=O)N)COP(=O)(O)OP(=O)(C(F)P(=O)(O)O)O)O | ||||
| InChI | 1S/C11H17FN5O12P3/c12-10(30(20,21)22)31(23,24)29-32(25,26)27-2-5-4(18)1-6(28-5)17-3-14-7-8(17)15-11(13)16-9(7)19/h3-6,10,18H,1-2H2,(H,23,24)(H,25,26)(H2,20,21,22)(H3,13,15,16,19)/t4-,5+,6+,10+/m0/s1 | ||||
| InChIKey | PVDLZOAYDIZEDJ-AVAJSQPUSA-N | ||||
| PubChem Compound ID | 135566320 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6NKV Ternary complex crystal structure of DNA polymerase Beta with "hot-spot sequence" with beta-gamma CHF analogue of dGTP | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [1] |
| PDB Sequence |
TLNGGITDML
19 TELANFEKNV29 SQAIHKYNAY39 RKAASVIAKY49 PHKIKSGAEA59 KKLPGVGTKI 69 AEKIDEFLAT79 GKLRKLEKIR89 QDDTSSSINF99 LTRVSGIGPS109 AARKFVDEGI 119 KTLEDLRKNE129 DKLNHHQRIG139 LKYFGDFEKR149 IPREEMLQMQ159 DIVLNEVKKV 169 DSEYIATVCG179 SFRRGAESSG189 DMDVLLTHPS199 FTSESTKQPK209 LLHQVVEQLQ 219 KVHFITDTLS229 KGETKFMGVC239 QLPSKNDEKE249 YPHRRIDIRL259 IPKDQYYCGV 269 LYFTGSDIFN279 KNMRAHALEK289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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| PDB ID: 4DO9 Ternary complex of dna polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-monofluoromethylene triphosphate: stereoselective binding of r-isomer | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [2] |
| PDB Sequence |
TLNGGITDML
19 TELANFEKNV29 SQAIHKYNAY39 RKAASVIAKY49 PHKIKSGAEA59 KKLPGVGTKI 69 AEKIDEFLAT79 GKLRKLEKIR89 QDDTSSSINF99 LTRVSGIGPS109 AARKFVDEGI 119 KTLEDLRKNE129 DKLNHHQRIG139 LKYFGDFEKR149 IPREEMLQMQ159 DIVLNEVKKV 169 DSEYIATVCG179 SFRRGAESSG189 DMDVLLTHPS199 FTSESTKQPK209 LLHQVVEQLQ 219 KVHFITDTLS229 KGETKFMGVC239 QLPSKNDEKE249 YPHRRIDIRL259 IPKDQYYCGV 269 LYFTGSDIFN279 KNMRAHALEK289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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| PDB ID: 6NKY Ternary complex crystal structure of K289M variant of DNA polymerase Beta with "hot-spot sequence" with beta-gamma CHF analogue of dGTP | ||||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | Yes | [1] |
| PDB Sequence |
TLNGGITDML
19 TELANFEKNV29 SQAIHKYNAY39 RKAASVIAKY49 PHKIKSGAEA59 KKLPGVGTKI 69 AEKIDEFLAT79 GKLRKLEKIR89 QDDTSSSINF99 LTRVSGIGPS109 AARKFVDEGI 119 KTLEDLRKNE129 DKLNHHQRIG139 LKYFGDFEKR149 IPREEMLQMQ159 DIVLNEVKKV 169 DSEYIATVCG179 SFRRGAESSG189 DMDVLLTHPS199 FTSESTKQPK209 LLHQVVEQLQ 219 KVHFITDTLS229 KGETKFMGVC239 QLPSKNDEKE249 YPHRRIDIRL259 IPKDQYYCGV 269 LYFTGSDIFN279 KNMRAHALEM289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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| PDB ID: 2PXI Ternary complex of DNA polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-monofluoromethylene triphosphate | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
TLNGGITDML
19 TELANFEKNV29 SQAIHKYNAY39 RKAASVIAKY49 PHKIKSGAEA59 KKLPGVGTKI 69 AEKIDEFLAT79 GKLRKLEKIR89 QDDTSSSINF99 LTRVSGIGPS109 AARKFVDEGI 119 KTLEDLRKNE129 DKLNHHQRIG139 LKYFGDFEKR149 IPREEMLQMQ159 DIVLNEVKKV 169 DSEYIATVCG179 SFRRGAESSG189 DMDVLLTHPS199 FTSESTKQPK209 LLHQVVEQLQ 219 KVHFITDTLS229 KGETKFMGVC239 QLPSKNDEKE249 YPHRRIDIRL259 IPKDQYYCGV 269 LYFTGSDIFN279 KNMRAHALEK289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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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 .GFH or .GFH2 or .GFH3 or :3GFH;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:183 or .A:188 or .A:189 or .A:190 or .A:192 or .A:256 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279 or .A:280 or .A:283; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6NKS Ternary complex crystal structure of K289M variant of DNA polymerase Beta with beta-gamma CHF analog of dGTP | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | Yes | [1] |
| PDB Sequence |
TLNGGITDML
19 TELANFEKNV29 SQAIHKYNAY39 RKAASVIAKY49 PHKIKSGAEA59 KKLPGVGTKI 69 AEKIDEFLAT79 GKLRKLEKIR89 QDDTSSSINF99 LTRVSGIGPS109 AARKFVDEGI 119 KTLEDLRKNE129 DKLNHHQRIG139 LKYFGDFEKR149 IPREEMLQMQ159 DIVLNEVKKV 169 DSEYIATVCG179 SFRRGAESSG189 DMDVLLTHPS199 FTSESTKQPK209 LLHQVVEQLQ 219 KVHFITDTLS229 KGETKFMGVC239 QLPSKNDEKE249 YPHRRIDIRL259 IPKDQYYCGV 269 LYFTGSDIFN279 KNMRAHALEM289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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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 .GFH or .GFH2 or .GFH3 or :3GFH;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:183 or .A:188 or .A:189 or .A:190 or .A:192 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279 or .A:280 or .A:283; 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 | Revealing an Internal Stabilization Deficiency in the DNA Polymerase beta K289M Cancer Variant through the Combined Use of Chemical Biology and X-ray Crystallography. Biochemistry. 2020 Mar 3;59(8):955-963. | ||||
| REF 2 | beta,Gamma-CHF- and beta,Gamma-CHCl-dGTP diastereomers: synthesis, discrete 31P NMR signatures, and absolute configurations of new stereochemical probes for DNA polymerases. J Am Chem Soc. 2012 May 30;134(21):8734-7. | ||||
| REF 3 | (R)-beta,gamma-fluoromethylene-dGTP-DNA ternary complex with DNA polymerase beta. J Am Chem Soc. 2007 Dec 19;129(50):15412-3. | ||||
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