View source for 4cpm


==Structure of the Neuraminidase from the B/Brisbane/60/2008 virus in complex with Oseltamivir==
<StructureSection load='4cpm' size='340' side='right'caption='[[4cpm]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cpm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Brisbane/60/2008) Influenza B virus (B/Brisbane/60/2008)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CPM 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]] 2.75&#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=EDO:1,2-ETHANEDIOL'>EDO</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=4cpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cpm OCA], [https://pdbe.org/4cpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cpm RCSB], [https://www.ebi.ac.uk/pdbsum/4cpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cpm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C0LT34_9INFB C0LT34_9INFB] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Introduction. Influenza B viruses with a novel I221 L substitution in neuraminidase (NA) conferring high level resistance to oseltamivir were isolated from an immunocompromised patient after prolonged oseltamivir treatment.Methods. Enzymatic characterization of the NAs (Km, Ki) and the in vitro fitness of viruses carrying wild-type (wt) or mutated (I221 L) NA genes were evaluated. Proportions of wt and mutated NA genes were directly quantified in the patient samples. Structural characterizations by X-ray crystallography of a wt and I221 L variant NA were performed.Results. The Km and Ki revealed that the I221 L variant NA had approximately 84 and 51 times lower affinity for oseltamivir carboxylate and zanamivir respectively compared to wt NA.Viruses with a wt or I221 L variant NA had similar growth kinetics in MDCK cells and five passages in MDCK cells revealed no reversion of the I221 L substitution. The crystal structure of the I221 L NA and oseltamivir complex showed that the leucine side-chain protrudes into the hydrophobic pocket of the active site that accommodates the pentyloxy substituent of oseltamivir.Conclusions. Enzyme kinetic and NA structural analyses provide an explanation for the high resistance to oseltamivir, while retaining good virus fitness of viruses carrying I221 L variant NA.

A novel I221 L substitution in neuraminidase confers high level resistance to oseltamivir in influenza B viruses.,Escuret V, Collins PJ, Casalegno JS, Vachieri SG, Cattle N, Ferraris O, Sabatier M, Frobert E, Caro V, Skehel JJ, Gamblin S, Valla F, Valette M, Ottmann M, McCauley JW, Daniels RS, Lina B J Infect Dis. 2014 May 3. PMID:24795482<ref>PMID:24795482</ref>

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

==See Also==
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Caro V]]
[[Category: Casalegno JS]]
[[Category: Cattle N]]
[[Category: Collins PJ]]
[[Category: Daniels RS]]
[[Category: Escuret V]]
[[Category: Ferraris O]]
[[Category: Frobert E]]
[[Category: Gamblin SJ]]
[[Category: Lina B]]
[[Category: McCauley JW]]
[[Category: Ottmann M]]
[[Category: Sabatier M]]
[[Category: Skehel JJ]]
[[Category: Vachieri SG]]
[[Category: Valette M]]
[[Category: Valla F]]