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| | <StructureSection load='2v4r' size='340' side='right'caption='[[2v4r]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2v4r' size='340' side='right'caption='[[2v4r]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2v4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sacs2 Sacs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V4R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2v4r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V4R 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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M1G:3-(2-DEOXY-BETA-D-RIBOFURANOSYL)-PYRIDO[5,6-A]-PURINE-10-ONE-5-MONOPHOSPHATE'>M1G</scene></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>, <scene name='pdbligand=M1G:3-(2-DEOXY-BETA-D-RIBOFURANOSYL)-PYRIDO[5,6-A]-PURINE-10-ONE-5-MONOPHOSPHATE'>M1G</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2asl|2asl]], [[1s0m|1s0m]], [[2jeg|2jeg]], [[1rys|1rys]], [[2j6t|2j6t]], [[1n56|1n56]], [[2atl|2atl]], [[1jx4|1jx4]], [[2c22|2c22]], [[2va2|2va2]], [[1s97|1s97]], [[2agq|2agq]], [[2jej|2jej]], [[2ago|2ago]], [[2asj|2asj]], [[2asd|2asd]], [[1n48|1n48]], [[1jxl|1jxl]], [[2bq3|2bq3]], [[2j6u|2j6u]], [[2uvu|2uvu]], [[2agp|2agp]], [[2c2r|2c2r]], [[1s0n|1s0n]], [[1s0o|1s0o]], [[2jef|2jef]], [[2uvw|2uvw]], [[2bqr|2bqr]], [[2jei|2jei]], [[2bqu|2bqu]], [[1s9f|1s9f]], [[2au0|2au0]], [[2c28|2c28]], [[2v9w|2v9w]], [[2c2e|2c2e]], [[1ryr|1ryr]], [[2c2d|2c2d]], [[2uvv|2uvv]], [[1s10|1s10]], [[2br0|2br0]], [[2j6s|2j6s]], [[2uvr|2uvr]], [[2va3|2va3]], [[2v4q|2v4q]], [[2v4s|2v4s]], [[2v4t|2v4t]]</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=2v4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4r OCA], [https://pdbe.org/2v4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v4r RCSB], [https://www.ebi.ac.uk/pdbsum/2v4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4r 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=2v4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4r OCA], [http://pdbe.org/2v4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v4r RCSB], [http://www.ebi.ac.uk/pdbsum/2v4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DPO4_SULSO DPO4_SULSO]] 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.[HAMAP-Rule:MF_01113] | + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sacs2]] | + | [[Category: Saccharolobus solfataricus P2]] |
| - | [[Category: Egli, M]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Eoff, R L]] | + | [[Category: Egli M]] |
| - | [[Category: Guengerich, F P]] | + | [[Category: Eoff RL]] |
| - | [[Category: Marnett, L J]] | + | [[Category: Guengerich FP]] |
| - | [[Category: Rizzo, C J]] | + | [[Category: Marnett LJ]] |
| - | [[Category: Stafford, J B]] | + | [[Category: Rizzo CJ]] |
| - | [[Category: Szekely, J]] | + | [[Category: Stafford JB]] |
| - | [[Category: Cytoplasm]]
| + | [[Category: Szekely J]] |
| - | [[Category: Dna adduct]]
| + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Dna-directed dna polymerase]]
| + | |
| - | [[Category: Dpo4]]
| + | |
| - | [[Category: M1dg]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Mutator protein]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
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| - | [[Category: Transferase]]
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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
Oxidative stress can induce the formation of reactive electrophiles, such as DNA peroxidation products, e.g. base propenals, and lipid peroxidation products, e.g. malondialdehyde. Base propenals and malondialdehyde react with DNA to form adducts, including 3-(2'-deoxy-ss-D-erythro-pentofuranosyl)-pyrimido[1,2-alpha]purin-10(3H)-o ne (M1dG). When paired opposite cytosine in duplex DNA at physiological pH, M1dG undergoes ring opening to form N2-(3-oxo-1-propenyl)-dG (N2-OPdG). Previous work has shown that M1dG is mutagenic in bacteria and mammalian cells and that its mutagenicity in Escherichia coli is dependent on induction of the SOS response, indicating a role for translesion DNA polymerases in the bypass of M1dG. To probe the mechanism by which translesion polymerases bypass M1dG, kinetic and structural studies were conducted with a model Y-family DNA polymerase, Dpo4 from Sulfolobus solfataricus. Steady-state incorporation of dNTPs opposite M1dG was reduced 260- to 2,900-fold and exhibited a preference for dATP incorporation. LC-MS/MS analysis of the full-length extension products revealed a spectrum of products arising principally by incorporation of dC or dA opposite M1dG followed by partial or full-length extension. A greater proportion of -1 deletions were observed when dT was positioned 5' of M1dG. Two crystal structures were solved, including a "Type II" frameshift deletion complex and another complex with Dpo4 bound to a dC:M1dG pair located in the post-insertion context. Importantly, M1dG was in the ring-closed state in both structures and in the structure with dC opposite M1dG, the dC residue moved out of the Dpo4 active site, into the minor groove. The results are consistent with the reported mutagenicity of M1dG and illustrate how the lesion may affect replication events.
Structural and Functional Analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed Bypass of the Malondialdehyde-deoxyguanosine Adduct.,Eoff RL, Stafford JB, Szekely J, Rizzo CJ, Egli M, Guengerich FP, Marnett LJ Biochemistry. 2009 Jun 4. PMID:19492857[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Eoff RL, Stafford JB, Szekely J, Rizzo CJ, Egli M, Guengerich FP, Marnett LJ. Structural and Functional Analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed Bypass of the Malondialdehyde-deoxyguanosine Adduct. Biochemistry. 2009 Jun 4. PMID:19492857 doi:10.1021/bi9003588
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