2m2v: Difference between revisions
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==African Swine Fever Virus Pol X in the ternary complex with MgdGTP and DNA== | ==African Swine Fever Virus Pol X in the ternary complex with MgdGTP and DNA== | ||
<StructureSection load='2m2v' size='340' side='right' caption='[[2m2v]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2m2v' size='340' side='right'caption='[[2m2v]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2m2v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Asf Asf]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M2V OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2m2v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Asf Asf]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M2V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2M2V FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m2t|2m2t]], [[2m2u|2m2u]], [[2m2w|2m2w]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m2t|2m2t]], [[2m2u|2m2u]], [[2m2w|2m2w]]</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='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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2m2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m2v OCA], [http://pdbe.org/2m2v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m2v RCSB], [http://www.ebi.ac.uk/pdbsum/2m2v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2m2v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 2m2v" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2m2v" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Asf]] | [[Category: Asf]] | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Large Structures]] | |||
[[Category: Su, M]] | [[Category: Su, M]] | ||
[[Category: Tsai, M]] | [[Category: Tsai, M]] | ||
Revision as of 09:18, 13 May 2020
African Swine Fever Virus Pol X in the ternary complex with MgdGTP and DNAAfrican Swine Fever Virus Pol X in the ternary complex with MgdGTP and DNA
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 PubMedA 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 AlsoReferences
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