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| | <StructureSection load='2jef' size='340' side='right'caption='[[2jef]], [[Resolution|resolution]] 2.17Å' scene=''> | | <StructureSection load='2jef' size='340' side='right'caption='[[2jef]], [[Resolution|resolution]] 2.17Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jef]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Sacs2 Sacs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JEF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jef]] 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=2JEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JEF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 2.17Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZG:6-(BENZYLOXY)-9-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-9H-PURIN-2-AMINE'>BZG</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BZG:6-(BENZYLOXY)-9-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-9H-PURIN-2-AMINE'>BZG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[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]], [[2asd|2asd]], [[2asj|2asj]], [[2asl|2asl]], [[2atl|2atl]], [[2au0|2au0]], [[2bq3|2bq3]], [[2bqr|2bqr]], [[2bqu|2bqu]], [[2br0|2br0]], [[2c22|2c22]], [[2c28|2c28]], [[2c2d|2c2d]], [[2c2e|2c2e]], [[2c2r|2c2r]], [[2j6s|2j6s]], [[2j6t|2j6t]], [[2j6u|2j6u]], [[2jeg|2jeg]], [[2jei|2jei]], [[2jej|2jej]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2jef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jef OCA], [https://pdbe.org/2jef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jef RCSB], [https://www.ebi.ac.uk/pdbsum/2jef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jef ProSAT]</span></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=2jef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jef OCA], [https://pdbe.org/2jef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jef RCSB], [https://www.ebi.ac.uk/pdbsum/2jef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jef 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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| | </div> | | </div> |
| | <div class="pdbe-citations 2jef" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2jef" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Large Structures]] |
| - | [[Category: Sacs2]] | + | [[Category: Saccharolobus solfataricus P2]] |
| - | [[Category: Angel, K C]] | + | [[Category: Angel KC]] |
| - | [[Category: Egli, M]] | + | [[Category: Egli M]] |
| - | [[Category: Eoff, R L]] | + | [[Category: Eoff RL]] |
| - | [[Category: Guengerich, F P]] | + | [[Category: Guengerich FP]] |
| - | [[Category: Kosekov, I D]] | + | [[Category: Kosekov ID]] |
| - | [[Category: Alkylating agent]]
| + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Dna-directed dna polymerase]]
| + | |
| - | [[Category: Dpo4]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Mutator protein]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| - | [[Category: Translesion synthesis]]
| + | |
| 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
Previous work has shown that Sulfolobus solfataricus DNA polymerase Dpo4-catalyzed bypass of O(6)-methylguanine (O(6)-MeG) proceeds largely in an accurate but inefficient manner with a "wobble" base pairing between C and O(6)-MeG (Eoff, R. L., Irimia, A., Egli, M., and Guengerich, F. P. (2007) J. Biol. Chem. 282, 1456-1467). We considered here the bulky lesion O(6)-benzylguanine (O(6)-BzG) in DNA and catalysis by Dpo4. Mass spectrometry analysis of polymerization products revealed that the enzyme bypasses and extends across from O(6)-BzG, with C the major product ( approximately 70%) and some T and A ( approximately 15% each) incorporated opposite the lesion. Steady-state kinetic parameters indicated that Dpo4 was 7-, 5-, and 27-fold more efficient at C incorporation opposite O(6)-BzG than T, A, or G, respectively. In transient state kinetic analysis, the catalytic efficiency was decreased 62-fold for C incorporation opposite O(6)-BzG relative to unmodified DNA. Crystal structures reveal wobble pairing between C and O(6)-BzG. Pseudo-"Watson-Crick" pairing was observed between T and O(6)-BzG. Two other structures illustrate a possible mechanism for the accommodation of a +1 frameshift in the Dpo4 active site. The overall effect of O(6)-BzG is to decrease the efficiency of bypass by roughly an order of magnitude in every case except correct bypass, where the effect is not as pronounced. By comparison, Dpo4 is more accurate but no more efficient than model replicative polymerases, such as bacteriophage T7(-) DNA polymerase and human immunodeficiency virus-1 reverse transcriptase in the polymerization past O(6)-MeG and O(6)-BzG.
Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing.,Eoff RL, Angel KC, Egli M, Guengerich FP J Biol Chem. 2007 May 4;282(18):13573-84. Epub 2007 Mar 3. PMID:17337730[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Eoff RL, Angel KC, Egli M, Guengerich FP. Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing. J Biol Chem. 2007 May 4;282(18):13573-84. Epub 2007 Mar 3. PMID:17337730 doi:http://dx.doi.org/10.1074/jbc.M700656200
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