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<StructureSection load='4cbh' size='340' side='right'caption='[[4cbh]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
<StructureSection load='4cbh' size='340' side='right'caption='[[4cbh]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4cbh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Classical_swine_fever_virus Classical swine fever virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CBH FirstGlance]. <br>
<table><tr><td colspan='2'>[[4cbh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Classical_swine_fever_virus Classical swine fever virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CBH FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cbg|4cbg]], [[4cbi|4cbi]], [[4cbl|4cbl]], [[4cbm|4cbm]]</td></tr>
</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=4cbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbh OCA], [https://pdbe.org/4cbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cbh RCSB], [https://www.ebi.ac.uk/pdbsum/4cbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbh ProSAT]</span></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=4cbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbh OCA], [http://pdbe.org/4cbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cbh RCSB], [http://www.ebi.ac.uk/pdbsum/4cbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbh ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/POLG_CSFVA POLG_CSFVA]] E(rns), E1 and E2 are responsible of cell attachment and subsequent fusion of viral and cellular membrane.  P7 forms a leader sequence to properly orient NS2 in the membrane.  Uncleaved NS2-3 is required for production of infectious virus.  NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus.[PROSITE-ProRule:PRU01029]  NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase.  NS4A is a cofactor for the NS3 protease activity.  RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome.[PROSITE-ProRule:PRU00539]  
[[https://www.uniprot.org/uniprot/POLG_CSFVA POLG_CSFVA]] E(rns), E1 and E2 are responsible of cell attachment and subsequent fusion of viral and cellular membrane.  P7 forms a leader sequence to properly orient NS2 in the membrane.  Uncleaved NS2-3 is required for production of infectious virus.  NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus.[PROSITE-ProRule:PRU01029]  NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase.  NS4A is a cofactor for the NS3 protease activity.  RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome.[PROSITE-ProRule:PRU00539]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of the non-structural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at 2.5 A resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, which contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses with deleted core protein map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with small angle X-ray scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a non-hydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. IMPORTANCE: Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the non-structural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and the hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the unwinding specificity of pNS3h, which is only active on RNA duplexes. We also show that pNS3h has a highly dynamic behavior - a characteristic probably shared with NS3 helicases from all Flaviviridae members - that could be targeted for drug design by using recent algorithms to specifically block molecular motion. Compounds that lock the enzyme in a single conformation, or limit its dynamic range of conformations are indeed likely to block its helicase function.


X-ray structure of the pestivirus NS3 helicase and its conformation in solution.,Tortorici MA, Duquerroy S, Kwok J, Vonrhein C, Perez J, Lamp B, Bricogne G, Rumenapf T, Vachette P, Rey FA J Virol. 2015 Feb 4. pii: JVI.03165-14. PMID:25653438<ref>PMID:25653438</ref>
==See Also==
 
*[[Nonstructural protein 3D structures|Nonstructural protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cbh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Classical swine fever virus]]
[[Category: Classical swine fever virus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bricogne, G]]
[[Category: Bricogne G]]
[[Category: Duquerroy, S]]
[[Category: Duquerroy S]]
[[Category: Kwok, J]]
[[Category: Kwok J]]
[[Category: Lamp, B]]
[[Category: Lamp B]]
[[Category: Perez, J]]
[[Category: Perez J]]
[[Category: Rey, F A]]
[[Category: Rey FA]]
[[Category: Rumenapf, T]]
[[Category: Rumenapf T]]
[[Category: Tortorici, M A]]
[[Category: Tortorici MA]]
[[Category: Vachette, P]]
[[Category: Vachette P]]
[[Category: Vonrhein, C]]
[[Category: Vonrhein C]]
[[Category: Flaviviridae ns3]]
[[Category: Hydrolase]]
[[Category: Sax]]
[[Category: Sf2 helicase]]

Revision as of 20:36, 7 September 2022

Pestivirus NS3 helicasePestivirus NS3 helicase

Structural highlights

4cbh is a 4 chain structure with sequence from Classical swine fever virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLG_CSFVA] E(rns), E1 and E2 are responsible of cell attachment and subsequent fusion of viral and cellular membrane. P7 forms a leader sequence to properly orient NS2 in the membrane. Uncleaved NS2-3 is required for production of infectious virus. NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus.[PROSITE-ProRule:PRU01029] NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS4A is a cofactor for the NS3 protease activity. RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome.[PROSITE-ProRule:PRU00539]

See Also

4cbh, resolution 2.51Å

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