View source for 7v1g


==Crystal structure of Omsk hemorrhagic fever virus NS5 MTase (with a GMP-Arg28 adduct and in complex with SAM)==
<StructureSection load='7v1g' size='340' side='right'caption='[[7v1g]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7v1g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Omsk_hemorrhagic_fever_virus Omsk hemorrhagic fever virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V1G 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]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=7v1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v1g OCA], [https://pdbe.org/7v1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v1g RCSB], [https://www.ebi.ac.uk/pdbsum/7v1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v1g ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The positive-sense flavivirus RNA genome bears a cap 1 structure essential for RNA stability and viral protein translation, and the formation of cap 1 requires the virally encoded nonstructural protein NS5 harboring guanylyltransferase (GTase), cap guanine N7 methyltransferase (N7 MTase), and 5'-nucleotide ribose 2'-O MTase activities in its single-domain MTase module. Despite numerous MTase-containing structures reported, the structural evidence for a critical GMP-enzyme intermediate formation and RNA repositioning when transitioning among different reactions is missing. Here, we report 10 high-resolution MTase crystal structures of Omsk hemorrhagic fever virus (OHFV), a representative high-consequence tick-borne flavivirus, capturing previously unidentified GMP-arginine adduct structures and a rarely observed capped RNA conformation. These structures help us thread capping events in the canonical model with a structure-based hypothesis involving the flipping of the 5' nucleotide, while the observation of an m(7)GMP-arginine adduct is compatible with an alternate capping model that decouples the N7 and 2'-O methylation steps. IMPORTANCE The methyltransferase (MTase) domain of flavivirus NS5 is unique in harboring guanylyltransferase (GTase), N7 MTase, and 2'-O MTase activities, playing a central role in viral RNA capping. However, the detailed mechanisms of the multistep capping process remain elusive. Here, we report 10 crystal structures of a flavivirus MTase to help understand the guanylyl transfer from GTP to the GTase itself and the transition between guanylyl transfer and methylation steps. In particular, a previously unobserved GMP-arginine covalent intermediate was captured multiple times in MTase crystal soaking trials with GTP present in the soaking solution, supporting its role in bridging the guanylyl transfer from GTP to the GTase and subsequent transfer to the 5'-diphosphate RNA.

Crystal Structures of Flavivirus NS5 Guanylyltransferase Reveal a GMP-Arginine Adduct.,Jia H, Zhong Y, Peng C, Gong P J Virol. 2022 Jul 27;96(14):e0041822. doi: 10.1128/jvi.00418-22. Epub 2022 Jun , 27. PMID:35758665<ref>PMID:35758665</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7v1g" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Omsk hemorrhagic fever virus]]
[[Category: Gong P]]
[[Category: Jia H]]