View source for 2hu4


==N1 neuraminidase in complex with oseltamivir 2==
<StructureSection load='2hu4' size='340' side='right'caption='[[2hu4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hu4]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. The May 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Influenza Neuraminidase''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_5 10.2210/rcsb_pdb/mom_2009_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HU4 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G39:(3R,4R,5S)-4-(ACETYLAMINO)-5-AMINO-3-(PENTAN-3-YLOXY)CYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>G39</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=2hu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hu4 OCA], [https://pdbe.org/2hu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hu4 RCSB], [https://www.ebi.ac.uk/pdbsum/2hu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hu4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NRAM_I04A1 NRAM_I04A1] 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.[HAMAP-Rule:MF_04071]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design.,Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP, Blackburn GM, Hay AJ, Gamblin SJ, Skehel JJ Nature. 2006 Sep 7;443(7107):45-9. Epub 2006 Aug 16. PMID:16915235<ref>PMID:16915235</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2hu4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Influenza A virus]]
[[Category: Influenza Neuraminidase]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Blackburn GM]]
[[Category: Collins PJ]]
[[Category: Gamblin SJ]]
[[Category: Haire LF]]
[[Category: Hay AJ]]
[[Category: Lin YP]]
[[Category: Russell RJ]]
[[Category: Skehel JJ]]
[[Category: Stevens DJ]]