4zp6: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[4zp6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_B3 Coxsackievirus B3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZP6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.648&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4zp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zp6 OCA], [https://pdbe.org/4zp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zp6 RCSB], [https://www.ebi.ac.uk/pdbsum/4zp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zp6 ProSAT]</span></td></tr>
 </table>
 == Function ==
 [https://www.uniprot.org/uniprot/Q5UEA2_9ENTO Q5UEA2_9ENTO]
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Positive strand RNA viruses replicate via a virally encoded RNA-dependent RNA polymerase (RdRP) that uses a unique palm domain active site closure mechanism to establish the canonical two-metal geometry needed for catalysis. This mechanism allows these viruses to evolutionarily fine-tune their replication fidelity in order to create an appropriate distribution of genetic variants known as a quasispecies. Prior work has shown that mutations in conserved motif A drastically alter RdRP fidelity, which can be either increased or decreased depending on the viral polymerase background. In the work presented here we extend these studies to motif D, a region that forms the outer edge of the NTP entry channel where it may act as a nucleotide sensor to trigger active site closure. Crystallography, stopped-flow kinetics, quench-flow reactions, and infectious virus studies were used to characterize fifteen engineered mutations in coxsackievirus B3 polymerase. Mutations that interfere with the transport of the metal A Mg2+ ion into the active site had only minor effects on RdRP function, but the stacking interaction between Phe364 and Pro357, which is absolutely conserved in enteroviral polymerases, was found to be critical for processive elongation and virus growth. Mutating Phe364 to tryptophan resulted in a genetically stable high-fidelity virus variant with significantly reduced pathogenesis in mice. The data further illustrate the importance of the palm domain movement for RdRP active site closure and demonstrate that protein engineering can be used to alter viral polymerase function and attenuate virus growth and pathogenesis.
-Design of a Genetically Stable High-Fidelity Coxsackievirus B3 Polymerase That Attenuates Virus Growth in vivo.,McDonald S, Block A, Beaucourt S, Moratorio G, Vignuzzi M, Peersen OB J Biol Chem. 2016 May 2. pii: jbc.M116.726596. PMID:27137934<ref>PMID:27137934</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4zp6" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>