4mjv

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{{STRUCTURE_4mjv| PDB=4mjv | SCENE= }}
 
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===Influenza Neuraminidase in complex with a novel antiviral compound===
 
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{{ABSTRACT_PUBMED_24339250}}
 
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==Function==
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==Influenza Neuraminidase in complex with a novel antiviral compound==
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[[http://www.uniprot.org/uniprot/NRAM_I63A3 NRAM_I63A3]] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.
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<StructureSection load='4mjv' size='340' side='right'caption='[[4mjv]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4mjv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/duck/Ukraine/1/1963(H3N8)) Influenza A virus (A/duck/Ukraine/1/1963(H3N8))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MJV FirstGlance]. <br>
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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]] 2.65&#8491;</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=27V:(2E,5S,9R,10S)-10-(ACETYLAMINO)-2-IMINO-4-OXO-9-(PENTAN-3-YLOXY)-1-THIA-3-AZASPIRO[4.5]DEC-6-ENE-7-CARBOXYLIC+ACID'>27V</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjv OCA], [https://pdbe.org/4mjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mjv RCSB], [https://www.ebi.ac.uk/pdbsum/4mjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mjv ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have previously reported a potent neuraminidase inhibitor that comprises a carbocyclic analogue of zanamivir in which the hydrophilic glycerol side chain is replaced by the hydrophobic 3-pentyloxy group of oseltamivir. This hybrid inhibitor showed excellent inhibitory properties in the neuraminidase inhibition assay (Ki =0.46 nM; Ki (zanamivir) =0.16 nM) and in the viral replication inhibition assay in cell culture at 10-8 M. As part of this lead optimization, we now report a novel spirolactam that shows comparable inhibitory activity in the cell culture assay to that of our lead compound at 10-7 M. The compound was discovered serendipitously during the attempted synthesis of the isothiourea derivative of the original candidate. The X-ray crystal structure of the spirolactam in complex with the N8 subtype neuraminidase offers insight into the mode of inhibition.
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==About this Structure==
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Serendipitous Discovery of a Potent Influenza Virus A Neuraminidase Inhibitor.,Mohan S, Kerry PS, Bance N, Niikura M, Pinto BM Angew Chem Int Ed Engl. 2013 Dec 11. doi: 10.1002/anie.201308142. PMID:24339250<ref>PMID:24339250</ref>
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[[4mjv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJV OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024339250</ref><references group="xtra"/><references/>
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</div>
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[[Category: Exo-alpha-sialidase]]
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<div class="pdbe-citations 4mjv" style="background-color:#fffaf0;"></div>
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[[Category: Influenza a virus]]
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[[Category: Kerry, P S.]]
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==See Also==
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
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[[Category: Neuraminidase]]
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== References ==
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[[Category: Sialidase]]
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<references/>
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[[Category: Viral protein]]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Kerry PS]]

Current revision

Influenza Neuraminidase in complex with a novel antiviral compound

PDB ID 4mjv

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