4zpb: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:


==Coxsackievirus B3 Polymerase - F364W mutant==
==Coxsackievirus B3 Polymerase - F364W mutant==
<StructureSection load='4zpb' size='340' side='right' caption='[[4zpb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='4zpb' size='340' side='right'caption='[[4zpb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4zpb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZPB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4zpb]] 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=4ZPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZPB FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zp6|4zp6]], [[4zp7|4zp7]], [[4zp8|4zp8]], [[4zp9|4zp9]], [[4zpa|4zpa]], [[4zpc|4zpc]], [[4zpd|4zpd]], [[4zr3|4zr3]], [[4zr4|4zr4]]</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]] 1.797&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zpb OCA], [http://pdbe.org/4zpb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zpb RCSB], [http://www.ebi.ac.uk/pdbsum/4zpb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zpb 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=4zpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zpb OCA], [https://pdbe.org/4zpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zpb RCSB], [https://www.ebi.ac.uk/pdbsum/4zpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zpb ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q5UEA2_9ENTO Q5UEA2_9ENTO]
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>
==See Also==
 
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zpb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: McDonald, S M]]
[[Category: Coxsackievirus B3]]
[[Category: Peersen, O B]]
[[Category: Large Structures]]
[[Category: Rna-dependent rna polymerase]]
[[Category: McDonald SM]]
[[Category: Transferase]]
[[Category: Peersen OB]]

Latest revision as of 15:16, 6 March 2024

Coxsackievirus B3 Polymerase - F364W mutantCoxsackievirus B3 Polymerase - F364W mutant

Structural highlights

4zpb is a 1 chain structure with sequence from Coxsackievirus B3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.797Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q5UEA2_9ENTO

See Also

4zpb, resolution 1.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=4zpb&oldid=4080131"