6br6: Difference between revisions
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==N2 neuraminidase in complex with a novel antiviral compound== | |||
<StructureSection load='6br6' size='340' side='right'caption='[[6br6]], [[Resolution|resolution]] 2.04Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6br6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Perth/16/2009(H3N2)) Influenza A virus (A/Perth/16/2009(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BR6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.0398388Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=E3M:(2~{R},4~{S},5~{R},6~{R})-5-acetamido-4-azanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]oxane-2-sulfonic+acid'>E3M</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=6br6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6br6 OCA], [https://pdbe.org/6br6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6br6 RCSB], [https://www.ebi.ac.uk/pdbsum/6br6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6br6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/E0UY46_9INFA E0UY46_9INFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Influenza virus infection continues to cause significant, often severe, respiratory illness worldwide. A validated target for development of anti-influenza agents is the viral surface protein sialidase. In the current study, we have discovered a highly potent inhibitor of influenza virus sialidase, based on a novel sialosyl sulfonate template. The synthesised 3-guanidino sialosyl alpha-sulfonate, a sulfonozanamivir analogue, inhibits virus replication in vitro at a nanomolar level, comparable to that of anti-influenza drug zanamivir. Using protein X-ray crystallography we show that the sialosyl alpha-sulfonate template orients within the sialidase active site in a (1)C(4) chair conformation. The C1-sulfonate moiety forms crucial and strong-binding interactions with the active site's triarginyl cluster, while the 3-guanidino moiety significantly interacts with conserved active site residues. This sulfonozanamivir analogue provides a new direction in anti-influenza virus drug development. | |||
A Sulfonozanamivir Analogue has Potent Anti-influenza Virus Activity.,Hadhazi A, Li L, Bailly B, Maggioni A, Martin G, Dirr L, Dyason J, Thomson R, Gao G, Borbas A, Ve T, Pascolutti M, von Itzstein M ChemMedChem. 2018 Feb 17. doi: 10.1002/cmdc.201800092. PMID:29453852<ref>PMID:29453852</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6br6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Bailly B]] | |||
[[Category: Gao GF]] | |||
[[Category: Hadhazi A]] | |||
[[Category: Li LH]] | |||
[[Category: Pascolutti M]] | |||
[[Category: Thomson RJ]] | |||
[[Category: Ve T]] | |||
[[Category: Von Itzstein M]] | |||
Latest revision as of 11:57, 9 October 2024
N2 neuraminidase in complex with a novel antiviral compoundN2 neuraminidase in complex with a novel antiviral compound
Structural highlights
FunctionPublication Abstract from PubMedInfluenza virus infection continues to cause significant, often severe, respiratory illness worldwide. A validated target for development of anti-influenza agents is the viral surface protein sialidase. In the current study, we have discovered a highly potent inhibitor of influenza virus sialidase, based on a novel sialosyl sulfonate template. The synthesised 3-guanidino sialosyl alpha-sulfonate, a sulfonozanamivir analogue, inhibits virus replication in vitro at a nanomolar level, comparable to that of anti-influenza drug zanamivir. Using protein X-ray crystallography we show that the sialosyl alpha-sulfonate template orients within the sialidase active site in a (1)C(4) chair conformation. The C1-sulfonate moiety forms crucial and strong-binding interactions with the active site's triarginyl cluster, while the 3-guanidino moiety significantly interacts with conserved active site residues. This sulfonozanamivir analogue provides a new direction in anti-influenza virus drug development. A Sulfonozanamivir Analogue has Potent Anti-influenza Virus Activity.,Hadhazi A, Li L, Bailly B, Maggioni A, Martin G, Dirr L, Dyason J, Thomson R, Gao G, Borbas A, Ve T, Pascolutti M, von Itzstein M ChemMedChem. 2018 Feb 17. doi: 10.1002/cmdc.201800092. PMID:29453852[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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