4mju

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{{STRUCTURE_4mju| PDB=4mju | SCENE= }}
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==Influenza Neuraminidase in complex with a novel antiviral compound==
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===Influenza Neuraminidase in complex with a novel antiviral compound===
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<StructureSection load='4mju' size='340' side='right' caption='[[4mju]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24339250}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4mju]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/I63a3 I63a3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MJU FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=27S:(5R,9R,10S)-10-(ACETYLAMINO)-2-AMINO-4-OXO-9-(PENTAN-3-YLOXY)-1-THIA-3-AZASPIRO[4.5]DECA-2,6-DIENE-7-CARBOXYLIC+ACID'>27S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </span></td></tr>
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<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=4mju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mju OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mju RCSB], [http://www.ebi.ac.uk/pdbsum/4mju PDBsum]</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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==Function==
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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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[[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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4mju]] 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=4MJU OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:024339250</ref><references group="xtra"/><references/>
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*[[Neuraminidase|Neuraminidase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Exo-alpha-sialidase]]
[[Category: Exo-alpha-sialidase]]
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[[Category: Influenza a virus]]
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[[Category: I63a3]]
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[[Category: Kerry, P S.]]
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[[Category: Kerry, P S]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Neuraminidase]]
[[Category: Neuraminidase]]
[[Category: Sialidase]]
[[Category: Sialidase]]
[[Category: Viral protein]]
[[Category: Viral protein]]

Revision as of 18:37, 21 December 2014

Influenza Neuraminidase in complex with a novel antiviral compound

4mju, resolution 2.35Å

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