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-[({[difluoro(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)(F)P(=O)(O)O)O)O | ||||
| InChI | 1S/C11H16F2N5O12P3/c12-11(13,31(21,22)23)32(24,25)30-33(26,27)28-2-5-4(19)1-6(29-5)18-3-15-7-8(18)16-10(14)17-9(7)20/h3-6,19H,1-2H2,(H,24,25)(H,26,27)(H2,21,22,23)(H3,14,16,17,20)/t4-,5+,6+/m0/s1 | ||||
| InChIKey | BLHFKUNEUAHYSE-KVQBGUIXSA-N | ||||
| PubChem Compound ID | 135566283 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6NL0 Ternary complex crystal structure of K289M variant of DNA polymerase Beta with "hot-spot sequence" with beta-gamma CF2 analogue of dGTP | ||||||
| Method | X-ray diffraction | Resolution | 1.97 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: 2ISO Ternary complex of DNA Polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-difluoromethylene triphosphate | ||||||
| Method | X-ray diffraction | Resolution | 2.10 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: 6NKT Ternary complex crystal structure of K289M variant of DNA polymerase Beta with beta-gamma difluoro analogue of dGTP | ||||||
| Method | X-ray diffraction | Resolution | 2.60 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 FTSESPKLLH212 QVVEQLQKVH 222 FITDTLSKGE232 TKFMGVCQLP242 SDEKEYPHRR254 IDIRLIPKDQ264 YYCGVLYFTG 274 SDIFNKNMRA284 HALEMGFTIN294 EYTIRPLGVT304 GVAGEPLPVD314 SEKDIFDYIQ 324 WKYREPKDRS334 E
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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 | Modifying the beta,gamma leaving-group bridging oxygen alters nucleotide incorporation efficiency, fidelity, and the catalytic mechanism of DNA polymerase beta. Biochemistry. 2007 Jan 16;46(2):461-71. | ||||
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