View source for 8ile


==The crystal structure of dGTPalphaSe-Rp:DNApre-II:Pol X substrate ternary complex==
<StructureSection load='8ile' size='340' side='right'caption='[[8ile]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ile]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/African_swine_fever_virus_BA71V African swine fever virus BA71V] 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=8ILE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ILE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7Q6:[[(2R,3S,5R)-5-(2-azanyl-6-oxidanylidene-1H-purin-9-yl)-3-oxidanyl-oxolan-2-yl]methoxy-selanyl-phosphoryl]+phosphono+hydrogen+phosphate'>7Q6</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=8ile FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ile OCA], [https://pdbe.org/8ile PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ile RCSB], [https://www.ebi.ac.uk/pdbsum/8ile PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ile ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA synthesis catalyzed by DNA polymerase is essential for all life forms, and phosphodiester bond formation with phosphorus center inversion is a key step in this process. Herein, by using a single-selenium-atom-modified dNTP probe, we report a novel strategy to visualize the reaction stereochemistry and catalysis. We capture the before- and after-reaction states and provide explicit evidence of the center inversion and in-line attacking S(N)2 mechanism of DNA polymerization, while solving the diastereomer absolute configurations. Further, our kinetic and thermodynamic studies demonstrate that in the presence of Mg(2+) ions (or Mn(2+)), the binding affinity (K(m)) and reaction selectivity (k(cat)/K(m)) of dGTPalphaSe-Rp were 51.1-fold (or 19.5-fold) stronger and 21.8-fold (or 11.3-fold) higher than those of dGTPalphaSe-Sp, respectively, indicating that the diastereomeric Se-Sp atom was quite disruptive of the binding and catalysis. Our findings reveal that the third metal ion is much more critical than the other two metal ions in both substrate recognition and bond formation, providing insights into how to better design the polymerase inhibitors and discover the therapeutics.

Structural Insight into Polymerase Mechanism via a Chiral Center Generated with a Single Selenium Atom.,Qin T, Hu B, Zhao Q, Wang Y, Wang S, Luo D, Lyu J, Chen Y, Gan J, Huang Z Int J Mol Sci. 2023 Oct 30;24(21):15758. doi: 10.3390/ijms242115758. PMID:37958741<ref>PMID:37958741</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8ile" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: African swine fever virus BA71V]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Gan JH]]
[[Category: Huang Z]]
[[Category: Qin T]]