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 | 5'-O-[(R)-Hydroxy{[(R)-Hydroxy(Phosphonooxy)phosphoryl]amino}phosphoryl]thymidine | Ligand Info | |||
| Canonical SMILES | CC1=CN(C(=O)NC1=O)C2CC(C(O2)COP(=O)(NP(=O)(O)OP(=O)(O)O)O)O | ||||
| InChI | 1S/C10H18N3O13P3/c1-5-3-13(10(16)11-9(5)15)8-2-6(14)7(25-8)4-24-27(17,18)12-28(19,20)26-29(21,22)23/h3,6-8,14H,2,4H2,1H3,(H,11,15,16)(H2,21,22,23)(H3,12,17,18,19,20)/t6-,7+,8+/m0/s1 | ||||
| InChIKey | YRKUYVYMPXAOAT-XLPZGREQSA-N | ||||
| PubChem Compound ID | 454113 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6E3V Structure of human DNA polymerase beta complexed with 8OA in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 1.96 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: 4YN4 Structure of human DNA polymerase beta complexed with N7BG in the template opposite to incoming non-hydrolyzable dTTP WITH MANGANESE IN THE ACTIVE SITE | ||||||
| Method | X-ray diffraction | Resolution | 2.24 Å | Mutation | No | [2] |
| PDB Sequence |
PQETLNGGIT
16 DMLTELANFE26 KNVSQAIHKY36 NAYRKAASVI46 AKYPHKIKSG56 AEAKKLPGVG 66 TKIAEKIDEF76 LATGKLRKLE86 KIRQDDTSSS96 INFLTRVSGI106 GPSAARKFVD 116 EGIKTLEDLR126 KNEDKLNHHQ136 RIGLKYFGDF146 EKRIPREEML156 QMQDIVLNEV 166 KKVDSEYIAT176 VCGSFRRGAE186 SSGDMDVLLT196 HPSFTSESQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKNDEK248 EYPHRRIDIR258 LIPKDQYYCG 268 VLYFTGSDIF278 NKNMRAHALE288 KGFTINEYTI298 RPLGVTGVAG308 EPLPVDSEKD 318 IFDYIQWKYR328 EPKDRSE
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| PDB ID: 4Z6F Structure of human DNA polymerase beta 279NA mutant complexed with G in the template base paired with incoming non-hydrolyzable TTP and MANGANESE | ||||||
| Method | X-ray diffraction | Resolution | 2.44 Å | Mutation | Yes | [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 LYFTGSDIFA279 KNMRAHALEK289 GFTINEYTIR299 PLGVTGVAGE309 PLPVDSEKDI 319 FDYIQWKYRE329 PKDRSE
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| PDB ID: 4Z6D Structure of human DNA polymerase beta 279NA mutant complexed with G in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 2.51 Å | Mutation | Yes | [3] |
| PDB Sequence |
PQETLNGGIT
16 DMLTELANFE26 KNVSQAIHKY36 NAYRKAASVI46 AKYPHKIKSG56 AEAKKLPGVG 66 TKIAEKIDEF76 LATGKLRKLE86 KIRQDDTSSS96 INFLTRVSGI106 GPSAARKFVD 116 EGIKTLEDLR126 KNEDKLNHHQ136 RIGLKYFGDF146 EKRIPREEML156 QMQDIVLNEV 166 KKVDSEYIAT176 VCGSFRRGAE186 SSGDMDVLLT196 HPSFTSESQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKNDEK248 EYPHRRIDIR258 LIPKDQYYCG 268 VLYFTGSDIF278 AKNMRAHALE288 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4Z6E Structure of human DNA polymerase beta 279NA mutant complexed with G in the template base paired with incoming non-hydrolyzable TTP and MANGANESE | ||||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | Yes | [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 LYFTGSDIFA279 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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:256 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 7MZ4 Structure of human DNA polymerase beta complexed with 3-deaza-3-methyladenine (3dMeA) in the template base paired with incoming dTTP | ||||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | No | [4] |
| PDB Sequence |
PQETLNGGIT
16 DMLTELANFE26 KNVSQAIHKY36 NAYRKAASVI46 AKYPHKIKSG56 AEAKKLPGVG 66 TKIAEKIDEF76 LATGKLRKLE86 KIRQDDTSSS96 INFLTRVSGI106 GPSAARKFVD 116 EGIKTLEDLR126 KNEDKLNHHQ136 RIGLKYFGDF146 EKRIPREEML156 QMQDIVLNEV 166 KKVDSEYIAT176 VCGSFRRGAE186 SSGDMDVLLT196 HPSFTSESQP208 KLLHQVVEQL 218 QKVHFITDTL228 SKGETKFMGV238 CQLPSKDEKE249 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4PGQ Structure of human DNA polymerase beta complexed with G in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 2.30 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 SFTSESQPKL210 LHQVVEQLQK 220 VHFITDTLSK230 GETKFMGVCQ240 LPSKDEKEYP251 HRRIDIRLIP261 KDQYYCGVLY 271 FTGSDIFNKN281 MRAHALEKGF291 TINEYTIRPL301 GVTGVAGEPL311 PVDSEKDIFD 321 YIQWKYREPK331 DRSE
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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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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:258 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 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: 4O5E Structure of human DNA polymerase complexed with N7MG in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 2.53 Å | Mutation | No | [6] |
| PDB Sequence |
PQETLNGGIT
16 DMLTELANFE26 KNVSQAIHKY36 NAYRKAASVI46 AKYPHKIKSG56 AEAKKLPGVG 66 TKIAEKIDEF76 LATGKLRKLE86 KIRQDDTSSS96 INFLTRVSGI106 GPSAARKFVD 116 EGIKTLEDLR126 KNEDKLNHHQ136 RIGLKYFGDF146 EKRIPREEML156 QMQDIVLNEV 166 KKVDSEYIAT176 VCGSFRRGAE186 SSGDMDVLLT196 HPSFTSESQP208 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4P2H Structure of human DNA polymerase complexed with N7MG in the template opposite to incoming non-hydrolyzable TTP with manganese in the active site | ||||||
| Method | X-ray diffraction | Resolution | 1.99 Å | Mutation | No | [6] |
| 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 FTSESQPKLL211 HQVVEQLQKV 221 HFITDTLSKG231 ETKFMGVCQL241 PSKNDEKEYP251 HRRIDIRLIP261 KDQYYCGVLY 271 FTGSDIFNKN281 MRAHALEKGF291 TINEYTIRPL301 GVTGVAGEPL311 PVDSEKDIFD 321 YIQWKYREPK331 DRSE
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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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4PGX Structure of human DNA polymerase beta complexed with G in the template base paired with incoming non-hydrolyzable TTP and MANGANESE | ||||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | No | [5] |
| 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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:256 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 7MZ1 Structure of human DNA polymerase beta complexed with dzA in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 2.17 Å | Mutation | No | [7] |
| 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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:256 or .A:271 or .A:272 or .A:273 or .A:274 or .A:275 or .A:276 or .A:279; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4NXZ DNA polymerase beta with O6mG in the template base opposite to incoming non-hydrolyzable TTP with manganese in the active site | ||||||
| Method | X-ray diffraction | Resolution | 2.56 Å | Mutation | No | [8] |
| 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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;style chemicals stick;color identity;select .A:40 or .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; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4MFF Structure of human DNA polymerase beta complexed with O6MG in the template base paired with incoming non-hydrolyzable TTP | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [8] |
| PDB Sequence |
LNGGITDMLT
20 ELANFEKNVS30 QAIHKYNAYR40 KAASVIAKYP50 HKIKSGAEAK60 KLPGVGTKIA 70 EKIDEFLATG80 KLRKLEKIRQ90 DDTSSSINFL100 TRVSGIGPSA110 ARKFVDEGIK 120 TLEDLRKNED130 KLNHHQRIGL140 KYFGDFEKRI150 PREEMLQMQD160 IVLNEVKKVD 170 SEYIATVCGS180 FRRGAESSGD190 MDVLLTHPSF200 TSESPKLLHQ213 VVEQLQKVHF 223 ITDTLSKGET233 KFMGVCQLPS243 KDEKEYPHRR254 IDIRLIPKDQ264 YYCGVLYFTG 274 SDIFNKNMRA284 HALEKGFTIN294 EYTIRPLGVT304 GVAGEPLPVD314 SEKDIFDYIQ 324 WKYREPKDRS334 E
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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 .1FZ or .1FZ2 or .1FZ3 or :31FZ;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; 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 | Mutagenic Replication of the Major Oxidative Adenine Lesion 7,8-Dihydro-8-oxoadenine by Human DNA Polymerases. J Am Chem Soc. 2019 Mar 20;141(11):4584-4596. | ||||
| REF 2 | Structural and Kinetic Studies of the Effect of Guanine N7 Alkylation and Metal Cofactors on DNA Replication. Biochemistry. 2018 Aug 28;57(34):5105-5116. | ||||
| REF 3 | Insights into the effect of minor groove interactions and metal cofactors on mutagenic replication by human DNA polymerase beta. Biochem J. 2018 Feb 9;475(3):571-585. | ||||
| REF 4 | Structure of human DNA polymerase beta complexed with 3-deaza-3-methyladenine (3dMeA) in the template base paired with incoming dTTP | ||||
| REF 5 | The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta. Nucleic Acids Res. 2014;42(17):11233-45. | ||||
| REF 6 | Transition-state destabilization reveals how human DNA polymerase beta proceeds across the chemically unstable lesion N7-methylguanine. Nucleic Acids Res. 2014 Jul;42(13):8755-66. | ||||
| REF 7 | Structure of human DNA polymerase beta complexed with dzA in the template base paired with incoming non-hydrolyzable TTP | ||||
| REF 8 | Metal-dependent conformational activation explains highly promutagenic replication across O6-methylguanine by human DNA polymerase beta. J Am Chem Soc. 2014 Apr 16;136(15):5709-21. | ||||
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