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3o9k

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Revision as of 10:42, 4 August 2016

Influenza NA in complex with compound 6

Structural highlights

3o9k is a 1 chain structure with sequence from I63a3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Exo-alpha-sialidase, with EC number 3.2.1.18
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

Influenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.,Rudrawar S, Dyason JC, Rameix-Welti MA, Rose FJ, Kerry PS, Russell RJ, van der Werf S, Thomson RJ, Naffakh N, von Itzstein M Nat Commun. 2010 Nov;1(8):113. Epub 2010 Nov 16. PMID:21081911^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rudrawar S, Dyason JC, Rameix-Welti MA, Rose FJ, Kerry PS, Russell RJ, van der Werf S, Thomson RJ, Naffakh N, von Itzstein M. Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase. Nat Commun. 2010 Nov;1(8):113. Epub 2010 Nov 16. PMID:21081911 doi:10.1038/ncomms1114

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o9k"

@@ Line 1: / Line 1: @@
 ==Influenza NA in complex with compound 6==
 <StructureSection load='3o9k' size='340' side='right' caption='[[3o9k]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o9k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o9k]] 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=3O9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ETT:5-(ACETYLAMINO)-2,6-ANHYDRO-3,5-DIDEOXY-3-[(2E)-3-(4-METHYLPHENYL)PROP-2-EN-1-YL]-D-GLYCERO-D-GALACTO-NON-2-ENONIC+ACID'>ETT</scene></td></tr>
 <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>
-<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=3o9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o9k RCSB], [http://www.ebi.ac.uk/pdbsum/3o9k PDBsum]</span></td></tr>
+<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=3o9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9k OCA], [http://pdbe.org/3o9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o9k RCSB], [http://www.ebi.ac.uk/pdbsum/3o9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o9k ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3o9k" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Exo-alpha-sialidase]]
-[[Category: Viruses]]
+[[Category: I63a3]]
 [[Category: Kerry, P S]]
 [[Category: Russell, R J]]
 [[Category: Glycosidase]]
 [[Category: Hydrolase]]

3o9k

From Proteopedia

Revision as of 10:42, 4 August 2016

Influenza NA in complex with compound 6

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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