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| | ==ASFV Pol X structure== | | ==ASFV Pol X structure== |
| - | <StructureSection load='2m2t' size='340' side='right'caption='[[2m2t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m2t' size='340' side='right'caption='[[2m2t]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m2t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Asf Asf]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M2T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m2t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/African_swine_fever_virus African swine fever virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M2T FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2m2u|2m2u]], [[2m2v|2m2v]], [[2m2w|2m2w]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m2t OCA], [https://pdbe.org/2m2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m2t RCSB], [https://www.ebi.ac.uk/pdbsum/2m2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m2t 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=2m2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m2t OCA], [https://pdbe.org/2m2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m2t RCSB], [https://www.ebi.ac.uk/pdbsum/2m2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m2t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DPOLX_ASFB7 DPOLX_ASFB7]] Error-prone polymerase lacking a proofreading 3'-5' exonuclease which plays a role in viral DNA repair. Specifically binds intermediates in the single-nucleotide base-excision repair process. Also catalyzes DNA polymerization with low nucleotide-insertion fidelity. Together with the viral DNA ligase, fills the single nucleotide gaps generated by the AP endonuclease.<ref>PMID:12595253</ref> <ref>PMID:11685239</ref>
| + | [https://www.uniprot.org/uniprot/DPOLX_ASFB7 DPOLX_ASFB7] Error-prone polymerase lacking a proofreading 3'-5' exonuclease which plays a role in viral DNA repair. Specifically binds intermediates in the single-nucleotide base-excision repair process. Also catalyzes DNA polymerization with low nucleotide-insertion fidelity. Together with the viral DNA ligase, fills the single nucleotide gaps generated by the AP endonuclease.<ref>PMID:12595253</ref> <ref>PMID:11685239</ref> |
| | <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 2m2t" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2m2t" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Asf]] | + | [[Category: African swine fever virus]] |
| - | [[Category: DNA-directed DNA polymerase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Su, M]] | + | [[Category: Su M]] |
| - | [[Category: Tsai, M]] | + | [[Category: Tsai M]] |
| - | [[Category: Wu, W]] | + | [[Category: Wu W]] |
| - | [[Category: Dna polymerase]]
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| - | [[Category: Nucleotidyl transferase]]
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| - | [[Category: Transferase]]
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| Structural highlights
Function
DPOLX_ASFB7 Error-prone polymerase lacking a proofreading 3'-5' exonuclease which plays a role in viral DNA repair. Specifically binds intermediates in the single-nucleotide base-excision repair process. Also catalyzes DNA polymerization with low nucleotide-insertion fidelity. Together with the viral DNA ligase, fills the single nucleotide gaps generated by the AP endonuclease.[1] [2]
Publication Abstract from PubMed
A dogma for DNA polymerase catalysis is that the enzyme binds DNA first, followed by MgdNTP. This mechanism contributes to the selection of correct dNTP by Watson-Crick base pairing, but it cannot explain how low-fidelity DNA polymerases overcome Watson-Crick base pairing to catalyze non-Watson-Crick dNTP incorporation. DNA polymerase X from the deadly African swine fever virus (Pol X) is a half-sized repair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair. Here we report the use of solution structures of Pol X in the free, binary (Pol X:MgdGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson-Crick pairing) forms, along with functional analyses, to show that Pol X uses multiple unprecedented strategies to achieve the mutagenic dG:dGTP incorporation. Unlike high fidelity polymerases, Pol X can prebind purine MgdNTP tightly and undergo a specific conformational change in the absence of DNA. The prebound MgdGTP assumes an unusual syn conformation stabilized by partial ring stacking with His115. Upon binding of a gapped DNA, also with a unique mechanism involving primarily helix alphaE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-dG. Interestingly, while Pol X prebinds MgdCTP weakly, the correct dG:dCTP ternary complex is readily formed in the presence of DNA. H115A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary complex formation. The results demonstrate the first solution structural view of DNA polymerase catalysis, a unique DNA binding mode, and a novel mechanism for non-Watson-Crick incorporation by a low-fidelity DNA polymerase.
How a Low-Fidelity DNA Polymerase Chooses Non-Watson-Crick from Watson-Crick Incorporation.,Wu WJ, Su MI, Wu JL, Kumar S, Lim LH, Wang CW, Nelissen FH, Chen MC, Doreleijers JF, Wijmenga SS, Tsai MD J Am Chem Soc. 2014 Mar 21. PMID:24617852[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garcia-Escudero R, Garcia-Diaz M, Salas ML, Blanco L, Salas J. DNA polymerase X of African swine fever virus: insertion fidelity on gapped DNA substrates and AP lyase activity support a role in base excision repair of viral DNA. J Mol Biol. 2003 Mar 7;326(5):1403-12. PMID:12595253
- ↑ Showalter AK, Byeon IJ, Su MI, Tsai MD. Solution structure of a viral DNA polymerase X and evidence for a mutagenic function. Nat Struct Biol. 2001 Nov;8(11):942-6. PMID:11685239 doi:10.1038/nsb1101-942
- ↑ Wu WJ, Su MI, Wu JL, Kumar S, Lim LH, Wang CW, Nelissen FH, Chen MC, Doreleijers JF, Wijmenga SS, Tsai MD. How a Low-Fidelity DNA Polymerase Chooses Non-Watson-Crick from Watson-Crick Incorporation. J Am Chem Soc. 2014 Mar 21. PMID:24617852 doi:http://dx.doi.org/10.1021/ja4102375
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