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==Crystal structure of influenza neuraminidase N3-H274Y complexed with oseltamivir== | |||
<StructureSection load='4hzz' size='340' side='right' caption='[[4hzz]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4hzz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/swine/missouri/2124514/2006(h2n3)) Influenza a virus (a/swine/missouri/2124514/2006(h2n3))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HZZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZZ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cl0|3cl0]], [[4hzv|4hzv]], [[4hzw|4hzw]], [[4hzx|4hzx]], [[4hzy|4hzy]], [[4i00|4i00]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=489926 Influenza A virus (A/swine/Missouri/2124514/2006(H2N3))])</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=4hzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hzz RCSB], [http://www.ebi.ac.uk/pdbsum/4hzz PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The influenza virus neuraminidase H274Y substitution is a highly prevalent amino acid substitution associated with resistance to the most heavily used influenza drug, oseltamivir. Previous structural studies suggest that the group specific 252 residue (Y252 in group 1 and T252 in group 2) might be a key factor underlying H274Y resistance. However, H274Y has only been reported in N1 subtypes, which indicates that there must be additional key residues that determine H274Y resistance. Furthermore, we found that members of NA serotype N3 also possess Y252, raising the key question as to whether or not H274Y resistance may also be possible for some group 2 NAs. Here, we demonstrate that the H274Y substitution results in mild oseltamivir resistance for N3. Comparative structural analysis of N3, N1, and their 274Y variants indicates that the interaction of residue 296 (H in N1 and nonaromatic for other serotypes) with conserved W295 is another important determinant of oseltamivir resistance. | |||
Functional and structural analysis of influenza virus neuraminidase N3 offers further insight into the mechanisms of oseltamivir resistance.,Li Q, Qi J, Wu Y, Kiyota H, Tanaka K, Suhara Y, Ohrui H, Suzuki Y, Vavricka CJ, Gao GF J Virol. 2013 Sep;87(18):10016-24. doi: 10.1128/JVI.01129-13. Epub 2013 Jul 3. PMID:23824808<ref>PMID:23824808</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Gao, G F | |||
[[Category: Li, Q | ==See Also== | ||
[[Category: Qi, J | *[[Neuraminidase|Neuraminidase]] | ||
[[Category: Vavricka, C J | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gao, G F]] | |||
[[Category: Li, Q]] | |||
[[Category: Qi, J]] | |||
[[Category: Vavricka, C J]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Neuraminidase]] | [[Category: Neuraminidase]] | ||
Revision as of 15:58, 21 December 2014
Crystal structure of influenza neuraminidase N3-H274Y complexed with oseltamivirCrystal structure of influenza neuraminidase N3-H274Y complexed with oseltamivir
Structural highlights
Publication Abstract from PubMedThe influenza virus neuraminidase H274Y substitution is a highly prevalent amino acid substitution associated with resistance to the most heavily used influenza drug, oseltamivir. Previous structural studies suggest that the group specific 252 residue (Y252 in group 1 and T252 in group 2) might be a key factor underlying H274Y resistance. However, H274Y has only been reported in N1 subtypes, which indicates that there must be additional key residues that determine H274Y resistance. Furthermore, we found that members of NA serotype N3 also possess Y252, raising the key question as to whether or not H274Y resistance may also be possible for some group 2 NAs. Here, we demonstrate that the H274Y substitution results in mild oseltamivir resistance for N3. Comparative structural analysis of N3, N1, and their 274Y variants indicates that the interaction of residue 296 (H in N1 and nonaromatic for other serotypes) with conserved W295 is another important determinant of oseltamivir resistance. Functional and structural analysis of influenza virus neuraminidase N3 offers further insight into the mechanisms of oseltamivir resistance.,Li Q, Qi J, Wu Y, Kiyota H, Tanaka K, Suhara Y, Ohrui H, Suzuki Y, Vavricka CJ, Gao GF J Virol. 2013 Sep;87(18):10016-24. doi: 10.1128/JVI.01129-13. Epub 2013 Jul 3. PMID:23824808[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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