4gb1
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gb1]] 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=4GB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GB1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gb1]] 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=4GB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GB1 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LP:5-(ACETYLAMINO)-2,6-ANHYDRO-3,5-DIDEOXY-3-[(2E)-3-PHENYLPROP-2-EN-1-YL]-D-GLYCERO-L-ALTRO-NON-2-ENONIC+ACID'>0LP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LP:5-(ACETYLAMINO)-2,6-ANHYDRO-3,5-DIDEOXY-3-[(2E)-3-PHENYLPROP-2-EN-1-YL]-D-GLYCERO-L-ALTRO-NON-2-ENONIC+ACID'>0LP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4gb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gb1 OCA], [https://pdbe.org/4gb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gb1 RCSB], [https://www.ebi.ac.uk/pdbsum/4gb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gb1 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=4gb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gb1 OCA], [https://pdbe.org/4gb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gb1 RCSB], [https://www.ebi.ac.uk/pdbsum/4gb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gb1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://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. | [https://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. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility. | ||
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| - | Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility.,Rudrawar S, Kerry PS, Rameix-Welti MA, Maggioni A, Dyason JC, Rose FJ, van der Werf S, Thomson RJ, Naffakh N, Russell RJ, von Itzstein M Org Biomol Chem. 2012 Sep 14. PMID:22976385<ref>PMID:22976385</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gb1" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | *[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 15:42, 14 March 2024
Synthesis and Evaluation of Novel 3-C-alkylated-Neu5Ac2en Derivatives as Probes of Influenza Virus Sialidase 150-loop flexibility
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