3upf

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nah|3nah]], [[3nai|3nai]], [[3uqs|3uqs]], [[3ur0|3ur0]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [https://pdbe.org/3upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [https://www.ebi.ac.uk/pdbsum/3upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf 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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [https://pdbe.org/3upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [https://www.ebi.ac.uk/pdbsum/3upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q80J95_9CALI Q80J95_9CALI]
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Caliciviridae are RNA viruses with a single-stranded, positively oriented polyadenylated genome, responsible for a broad spectrum of diseases such as acute gastroenteritis in humans. Recently, analyses on the structures and functionalities of the RNA-dependent RNA polymerase (RdRp) from several Caliciviruses have been reported. The RdRp is predicted to play a key role in genome replication, as well as in synthesis and amplification of additional subgenomic RNA. Starting from the crystal structures of human Norovirus (hNV) RdRp, we performed an in silico docking search to identify synthetic compounds with predicted high affinity for the enzyme active site. The best-ranked candidates were tested in vitro on murine Norovirus (MNV) and hNV RdRps to assay their inhibition of RNA polymerization. The results of such combined computational and experimental screening approach led to the identification of two high-potency inhibitors: Suramin and NF023, both symmetric divalent molecules hosting two naphthalene-trisulfonic acid heads. We report here the crystal structure of MNV RdRp alone and in the presence of the two identified inhibitors. Both inhibitory molecules occupy the same RdRp site, between the fingers and thumb domains, with one inhibitor head close to residue 42 and to the protein active site. To further validate the structural results, we mutated Trp42 to Ala in MNV RdRp and the corresponding residue (i.e., Tyr41 to Ala) in hNV RdRp. Both NF023 and Suramin displayed reduced inhibitory potency versus the mutated hNV RdRp, thus hinting at a conserved inhibitor binding mode in the two polymerases.
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Structure-Based Inhibition of Norovirus RNA-Dependent RNA Polymerases.,Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M J Mol Biol. 2012 Mar 21. PMID:22446684<ref>PMID:22446684</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3upf" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Murine norovirus 1]]
[[Category: Murine norovirus 1]]
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[[Category: Bolognesi, M]]
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[[Category: Bolognesi M]]
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[[Category: Mastrangelo, E]]
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[[Category: Mastrangelo E]]
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[[Category: Milani, M]]
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[[Category: Milani M]]
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[[Category: Murine norovirus]]
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[[Category: Rna-dependent rna polymerase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023

PDB ID 3upf

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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