View source for 4qpx


==NV polymerase post-incorporation-like complex==
<StructureSection load='4qpx' size='340' side='right'caption='[[4qpx]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qpx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Norwalk_virus Norwalk virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QPX 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]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4qpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qpx OCA], [https://pdbe.org/4qpx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qpx RCSB], [https://www.ebi.ac.uk/pdbsum/4qpx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qpx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q70ET3_9CALI Q70ET3_9CALI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The RNA-dependent RNA polymerase (RdRP) from norovirus (NV) genogroup II has previously been crystallized as an apoenzyme (APO1) in multiple crystal forms, as well as as a pre-incorporation ternary complex (PRE1) bound to Mn(2+), various nucleoside triphosphates and an RNA primer-template duplex in an orthorhombic crystal form. When crystallized under near-identical conditions with a slightly different RNA primer/template duplex, however, the enzyme-RNA complex forms tetragonal crystals (anisotropic data, dmin approximately 1.9 A) containing a complex with the primer/template bound in a backtracked state (BACK1) similar to a post-incorporation complex (POST1) in a step of the enzymatic cycle immediately following nucleotidyl transfer. The BACK1 conformation shows that the terminal nucleotide of the primer binds in a manner similar to the nucleoside triphosphate seen in the PRE1 complex, even though the terminal two phosphoryl groups in the triphosphate moiety are absent and a covalent bond is present between the alpha-phosphoryl group of the terminal nucleotide and the 3'-oxygen of the penultimate nucleotide residue. The two manganese ions bound at the active site coordinate to conserved Asp residues and the bridging phosphoryl group of the terminal nucleotide. Surprisingly, the conformation of the thumb domain in BACK1 resembles the open APO1 state more than the closed conformation seen in PRE1. The BACK1 complex thus reveals a hybrid state in which the active site is closed while the thumb domain is open. Comparison of the APO1, PRE1 and BACK1 structures of NV polymerase helps to reveal a more complete and complex pathway of conformational changes within a single RdRP enzyme system. These conformational changes lend insight into the mechanism of RNA translocation following nucleotidyl transfer and suggest novel approaches for the development of antiviral inhibitors.

Structure of a backtracked state reveals conformational changes similar to the state following nucleotide incorporation in human norovirus polymerase.,Zamyatkin D, Rao C, Hoffarth E, Jurca G, Rho H, Parra F, Grochulski P, Ng KK Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3099-109. doi:, 10.1107/S1399004714021518. Epub 2014 Nov 22. PMID:25478829<ref>PMID:25478829</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qpx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Norwalk virus]]
[[Category: Grochulski P]]
[[Category: Ng KKS]]
[[Category: Parra F]]
[[Category: Zamyatkin DF]]