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| | ==Efficient and High Fidelity Incorporation of dCTP Opposite 7,8- Dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA Polymerase Dpo4== | | ==Efficient and High Fidelity Incorporation of dCTP Opposite 7,8- Dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA Polymerase Dpo4== |
| - | <StructureSection load='2c22' size='340' side='right' caption='[[2c22]], [[Resolution|resolution]] 2.56Å' scene=''> | + | <StructureSection load='2c22' size='340' side='right'caption='[[2c22]], [[Resolution|resolution]] 2.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2c22]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulso Sulso]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2C22 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2c22]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C22 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.56Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jx4|1jx4]], [[1jxl|1jxl]], [[1n48|1n48]], [[1n56|1n56]], [[1ryr|1ryr]], [[1rys|1rys]], [[1s0m|1s0m]], [[1s0n|1s0n]], [[1s0o|1s0o]], [[1s10|1s10]], [[1s97|1s97]], [[1s9f|1s9f]], [[2ago|2ago]], [[2agp|2agp]], [[2agq|2agq]], [[2bq3|2bq3]], [[2bqr|2bqr]], [[2bqu|2bqu]], [[2br0|2br0]], [[2c28|2c28]], [[2c2d|2c2d]], [[2c2e|2c2e]], [[2c2r|2c2r]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c22 OCA], [https://pdbe.org/2c22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c22 RCSB], [https://www.ebi.ac.uk/pdbsum/2c22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c22 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c22 OCA], [http://pdbe.org/2c22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2c22 RCSB], [http://www.ebi.ac.uk/pdbsum/2c22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2c22 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DPO4_SACS2 DPO4_SACS2] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[DNA polymerase|DNA polymerase]] | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Sulso]] | + | [[Category: Saccharolobus solfataricus P2]] |
| - | [[Category: Egli, M]] | + | [[Category: Egli M]] |
| - | [[Category: Irimia, A]] | + | [[Category: Irimia A]] |
| - | [[Category: Loukachevitch, L V]] | + | [[Category: Loukachevitch LV]] |
| - | [[Category: 8-dihydro-8-oxodeoxyguanosine]]
| + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Dna- binding]]
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| - | [[Category: Dna-directed dna polymerase]]
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| - | [[Category: Magnesium]]
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| - | [[Category: Metal - binding]]
| + | |
| - | [[Category: Mutator protein]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: P2 dna polymerase iv]]
| + | |
| - | [[Category: Polymerase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Translesion dna polymerase]]
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| Structural highlights
Function
DPO4_SACS2 Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
DNA polymerases insert dATP opposite the oxidative damage product 7,8-dihydro-8-oxodeoxyguanosine (8-oxoG) instead of dCTP, to the extent of >90% with some polymerases. Steady-state kinetics with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4) showed 90-fold higher incorporation efficiency of dCTP > dATP opposite 8-oxoG and 4-fold higher efficiency of extension beyond an 8-oxoG:C pair than an 8-oxoG:A pair. The catalytic efficiency for these events (with dCTP or C) was similar for G and 8-oxoG templates. Mass spectral analysis of extended DNA primers showed >/=95% incorporation of dCTP > dATP opposite 8-oxoG. Pre-steady-state kinetics showed faster rates of dCTP incorporation opposite 8-oxoG than G. The measured K(d)(,dCTP) was 15-fold lower for an oligonucleotide containing 8-oxoG than with G. Extension beyond an 8-oxoG:C pair was similar to G:C and faster than for an 8-oxoG:A pair, in contrast to other polymerases. The E(a) for dCTP insertion opposite 8-oxoG was lower than for opposite G. Crystal structures of Dpo4 complexes with oligonucleotides were solved with C, A, and G nucleoside triphosphates placed opposite 8-oxoG. With ddCTP, dCTP, and dATP the phosphodiester bonds were formed even in the presence of Ca(2+). The 8-oxoG:C pair showed classic Watson-Crick geometry; the 8-oxoG:A pair was in the syn:anti configuration, with the A hybridized in a Hoogsteen pair with 8-oxoG. With dGTP placed opposite 8-oxoG, pairing was not to the 8-oxoG but to the 5' C (and in classic Watson-Crick geometry), consistent with the low frequency of this frameshift event observed in the catalytic assays.
Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4.,Zang H, Irimia A, Choi JY, Angel KC, Loukachevitch LV, Egli M, Guengerich FP J Biol Chem. 2006 Jan 27;281(4):2358-72. Epub 2005 Nov 22. PMID:16306039[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zang H, Irimia A, Choi JY, Angel KC, Loukachevitch LV, Egli M, Guengerich FP. Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4. J Biol Chem. 2006 Jan 27;281(4):2358-72. Epub 2005 Nov 22. PMID:16306039 doi:http://dx.doi.org/10.1074/jbc.M510889200
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