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| | ==Dpo4 polymerase pre-insertion binary complex with the N-(deoxyguanosin-8-yl)-1-aminopyrene lesion== | | ==Dpo4 polymerase pre-insertion binary complex with the N-(deoxyguanosin-8-yl)-1-aminopyrene lesion== |
| - | <StructureSection load='4fbu' size='340' side='right' caption='[[4fbu]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4fbu' size='340' side='right'caption='[[4fbu]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fbu]] is a 6 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=4FBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FBU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fbu]] is a 6 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=4FBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FBU 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></td></tr> | + | </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=DG8:2-DEOXY-8-(PYREN-1-YLAMINO)GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>DG8</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DG8:2-DEOXY-8-(PYREN-1-YLAMINO)GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>DG8</scene></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=4fbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbu OCA], [https://pdbe.org/4fbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fbu RCSB], [https://www.ebi.ac.uk/pdbsum/4fbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbu ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fbt|4fbt]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dbh, dpo4, SSO2448 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273057 SULSO])</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=4fbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbu OCA], [http://pdbe.org/4fbu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fbu RCSB], [http://www.ebi.ac.uk/pdbsum/4fbu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbu 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4fbu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4fbu" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[DNA polymerase|DNA polymerase]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Sulso]] | + | [[Category: Saccharolobus solfataricus P2]] |
| - | [[Category: Basu, A]] | + | [[Category: Basu A]] |
| - | [[Category: Kirouac, K]] | + | [[Category: Kirouac K]] |
| - | [[Category: Ling, H]] | + | [[Category: Ling H]] |
| - | [[Category: Dna polymerase]]
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| - | [[Category: Transferase-dna complex]]
| + | |
| 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.
Publication Abstract from PubMed
Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties.
Structural Mechanism of Replication Stalling on a Bulky Amino-Polycyclic Aromatic Hydrocarbon DNA Adduct by a Y Family DNA Polymerase.,Kirouac KN, Basu AK, Ling H J Mol Biol. 2013 Jul 20. pii: S0022-2836(13)00454-3. doi:, 10.1016/j.jmb.2013.07.020. PMID:23876706[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kirouac KN, Basu AK, Ling H. Structural Mechanism of Replication Stalling on a Bulky Amino-Polycyclic Aromatic Hydrocarbon DNA Adduct by a Y Family DNA Polymerase. J Mol Biol. 2013 Jul 20. pii: S0022-2836(13)00454-3. doi:, 10.1016/j.jmb.2013.07.020. PMID:23876706 doi:10.1016/j.jmb.2013.07.020
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