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'-Deoxyguanosine-5'-triphosphate | Ligand Info | |||
| Canonical SMILES | C1C(C(OC1N2C=NC3=C2N=C(NC3=O)N)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O | ||||
| InChI | 1S/C10H16N5O13P3/c11-10-13-8-7(9(17)14-10)12-3-15(8)6-1-4(16)5(26-6)2-25-30(21,22)28-31(23,24)27-29(18,19)20/h3-6,16H,1-2H2,(H,21,22)(H,23,24)(H2,18,19,20)(H3,11,13,14,17)/t4-,5+,6+/m0/s1 | ||||
| InChIKey | HAAZLUGHYHWQIW-KVQBGUIXSA-N | ||||
| PubChem Compound ID | 135398599 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6NKU Ternary complex crystal structure of DNA polymerase Beta with "hot-spot sequence" with dGTP | ||||||
| Method | X-ray diffraction | Resolution | 1.90 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: 4UB4 DNA polymerase beta substrate complex with a templating cytosine and incoming dGTP, 0 s | ||||||
| Method | X-ray diffraction | Resolution | 1.95 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: 6NKX Ternary complex crystal structure of K289M variant of DNA polymerase Beta with "hot-spot sequence" with dGTP | ||||||
| Method | X-ray diffraction | Resolution | 1.98 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: 6NKR Ternary complex crystal structure of K289M variant of DNA polymerase Beta with dGTP | ||||||
| Method | X-ray diffraction | Resolution | 2.45 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 .DGT or .DGT2 or .DGT3 or :3DGT;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:183 or .A:187 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 #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1ZJN Human DNA Polymerase beta complexed with DNA containing an A-A mismatched primer terminus with dGTP | ||||||
| Method | X-ray diffraction | Resolution | 2.61 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 PKDRS
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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 .DGT or .DGT2 or .DGT3 or :3DGT;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:183 or .A:187 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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| PDB ID: 9ICH DNA POLYMERASE BETA (POL B) (E.C.2.7.7.7) COMPLEXED WITH SEVEN BASE PAIRS OF DNA; SOAKED IN THE PRESENCE OF DGTP (1 MILLIMOLAR) AND ZNCL2 (1 MILLIMOLAR) | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [4] |
| PDB Sequence |
ETLNGGITDM
18 LTELANFEKN28 VSQAIHKYNA38 YRKAASVIAK48 YPHKIKSGAE58 AKKLPGVGTK 68 IAEKIDEFLA78 TGKLRKLEKI88 RQDDTSSSIN98 FLTRVSGIGP108 SAARKFVDEG 118 IKTLEDLRKN128 EDKLNHHQRI138 GLKYFGDFEK148 RIPREEMLQM158 QDIVLNEVKK 168 VDSEYIATVC178 GSFRRGAESS188 GDMDVLLTHP198 SFTSESTKQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKNDEK248 EYPHRRIDIR258 LIPKDQYYCG 268 VLYFTGSDIF278 NKNMRAHALE288 KGFTINEYTI298 RPLGVTGVAG308 EPLPVDSEKD 318 IFDYIQWKYR328 EPKDRSE
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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 .DGT or .DGT2 or .DGT3 or :3DGT;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:181 or .A:183 or .A:187 or .A:188 or .A:189 or .A:190 or .A:192; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 9ICT DNA POLYMERASE BETA (E.C.2.7.7.7)/DNA COMPLEX + 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, SOAKED IN THE PRESENCE OF DGTP AND MNCL2 | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [5] |
| PDB Sequence |
ETLNGGITDM
18 LTELANFEKN28 VSQAIHKYNA38 YRKAASVIAK48 YPHKIKSGAE58 AKKLPGVGTK 68 IAEKIDEFLA78 TGKLRKLEKI88 RQDDTSSSIN98 FLTRVSGIGP108 SAARKFVDEG 118 IKTLEDLRKN128 EDKLNHHQRI138 GLKYFGDFEK148 RIPREEMLQM158 QDIVLNEVKK 168 VDSEYIATVC178 GSFRRGAESS188 GDMDVLLTHP198 SFTSESTKQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKNDEK248 EYPHRRIDIR258 LIPKDQYYCG 268 VLYFTGSDIF278 NKNMRAHALE288 KGFTINEYTI298 RPLGVTGVAG308 EPLPVDSEKD 318 IFDYIQWKYR328 EPKDRSE
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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 .DGT or .DGT2 or .DGT3 or :3DGT;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:181 or .A:183 or .A:187 or .A:188 or .A:189 or .A:190 or .A:192 or .A:272; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 8ICV DNA POLYMERASE BETA (POL B) (E.C.2.7.7.7) COMPLEXED WITH SEVEN BASE PAIRS OF DNA; SOAKED IN THE PRESENCE OF DGTP (1 MILLIMOLAR) AND MNCL2 (5 MILLIMOLAR) | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [5] |
| PDB Sequence |
ETLNGGITDM
18 LTELANFEKN28 VSQAIHKYNA38 YRKAASVIAK48 YPHKIKSGAE58 AKKLPGVGTK 68 IAEKIDEFLA78 TGKLRKLEKI88 RQDDTSSSIN98 FLTRVSGIGP108 SAARKFVDEG 118 IKTLEDLRKN128 EDKLNHHQRI138 GLKYFGDFEK148 RIPREEMLQM158 QDIVLNEVKK 168 VDSEYIATVC178 GSFRRGAESS188 GDMDVLLTHP198 SFTSESTKQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKNDEK248 EYPHRRIDIR258 LIPKDQYYCG 268 VLYFTGSDIF278 NKNMRAHALE288 KGFTINEYTI298 RPLGVTGVAG308 EPLPVDSEKD 318 IFDYIQWKYR328 EPKDRSE
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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 .DGT or .DGT2 or .DGT3 or :3DGT;style chemicals stick;color identity;select .A:149 or .A:179 or .A:180 or .A:183 or .A:187 or .A:188 or .A:189 or .A:190 or .A:192 or .A:272; 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 | 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 | Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide. Nature. 2015 Jan 29;517(7536):635-9. | ||||
| REF 3 | Nucleotide-induced DNA polymerase active site motions accommodating a mutagenic DNA intermediate. Structure. 2005 Aug;13(8):1225-33. | ||||
| REF 4 | Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis. Biochemistry. 1996 Oct 1;35(39):12778-87. | ||||
| REF 5 | A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta. Biochemistry. 1996 Oct 1;35(39):12762-77. | ||||
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