View source for 4gzp


==N2 Neuraminidase of A/Tanzania/205/2010 H3N2 in complex with oseltamivir carboxylate==
<StructureSection load='4gzp' size='340' side='right'caption='[[4gzp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gzp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/H3N2_subtype H3N2 subtype]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GZP 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]] 2.3&#8491;</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=G39:(3R,4R,5S)-4-(ACETYLAMINO)-5-AMINO-3-(PENTAN-3-YLOXY)CYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>G39</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4gzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gzp OCA], [https://pdbe.org/4gzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gzp RCSB], [https://www.ebi.ac.uk/pdbsum/4gzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gzp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/K7N5N3_9INFA K7N5N3_9INFA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Influenza neuraminidase (NA) cleaves off sialic acid from cellular receptors of hemagglutinin (HA) to enable progeny escape from infected cells. However, NA variants (D151G) of recent human H3N2 viruses have been reported to also bind receptors on red blood cells, but the nature of these receptors and the effect of the mutation on NA activity were not established. Here, we compare the functional and structural properties of a human H3N2 NA from A/Tanzania/205/2010 and its D151G mutant, which supports HA-independent receptor binding. While the wild-type NA efficiently cleaves sialic acid from both alpha2-6 and alpha2-3 linked glycans, the mutant exhibits much reduced enzymatic activity towards both types of sialosides. Conversely, while wild-type NA shows no detectable binding to sialosides, the D151G NA exhibits avid binding with broad specificity towards alpha2-3 sialosides. D151G NA binds sialosides 3' -SLN and 6' -SLN with K(D) values of 30.0 muM and 645 muM, respectively, which correspond to much higher affinities than HA to these glycans (K(D) approximately mM). Crystal structures of wild-type and mutant NAs reveal the structural basis for glycan binding in the active site by exclusively impairing the glycosidic bond hydrolysis step. The general significance of D151 among influenza was further explored by introducing the D151G mutation into three N1 and one other N2 NAs, which all exhibited reduced enzymatic activity, and also preferential binding to alpha2-3 sialosides. Since the enzymatic and binding activities of NAs are not routinely assessed, the potential for NA receptor binding to contribute to influenza biology may be underappreciated.

Influenza virus neuraminidases with reduced enzymatic activity that avidly bind sialic acid receptors.,Zhu X, McBride R, Nycholat CM, Yu W, Paulson JC, Wilson IA J Virol. 2012 Sep 26. PMID:23015718<ref>PMID:23015718</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gzp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: H3N2 subtype]]
[[Category: Large Structures]]
[[Category: Wilson IA]]
[[Category: Zhu X]]