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==Crystal Structure of B/Perth Neuraminidase D197E mutant in complex with Oseltamivir== | ==Crystal Structure of B/Perth Neuraminidase D197E mutant in complex with Oseltamivir== | ||
<StructureSection load='3k3a' size='340' side='right' caption='[[3k3a]], [[Resolution|resolution]] 2.59Å' scene=''> | <StructureSection load='3k3a' size='340' side='right' caption='[[3k3a]], [[Resolution|resolution]] 2.59Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3k3a]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3k3a]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus_(b/perth/211/2001) Influenza b virus (b/perth/211/2001)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K3A 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr> | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k36|3k36]], [[3k37|3k37]], [[3k38|3k38]], [[3k39|3k39]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k36|3k36]], [[3k37|3k37]], [[3k38|3k38]], [[3k39|3k39]]</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='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=3k3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k3a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k3a RCSB], [http://www.ebi.ac.uk/pdbsum/3k3a 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=3k3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k3a OCA], [http://pdbe.org/3k3a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k3a RCSB], [http://www.ebi.ac.uk/pdbsum/3k3a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k3a ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3k3a" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Exo-alpha-sialidase]] | [[Category: Exo-alpha-sialidase]] | ||
[[Category: McKimm-Breschkin, J L]] | [[Category: McKimm-Breschkin, J L]] | ||
[[Category: Oakley, A J]] | [[Category: Oakley, A J]] | ||
Revision as of 23:35, 9 December 2016
Crystal Structure of B/Perth Neuraminidase D197E mutant in complex with OseltamivirCrystal Structure of B/Perth Neuraminidase D197E mutant in complex with Oseltamivir
Structural highlights
Publication Abstract from PubMedWe have identified a virus, B/Perth/211/2001, with a spontaneous mutation, D197E in the neuraminidase (NA), which confers cross-resistance to all NA inhibitors. We analyzed enzyme properties of the D197 and E197 NAs and compared these to a D197N NA, known to arise after oseltamivir treatment. Zanamivir and peramivir bound slowly to the wild type NA, but binding of oseltamivir was more rapid. The D197E/N mutations resulted in faster binding of all three inhibitors. Analysis of the crystal structures of D197 and E197 NAs with and without inhibitors showed that the D197E mutation compromised the interaction of neighboring R150 with the N-acetyl group, common to the substrate sialic acid and all NA inhibitors. Although rotation of the E275 in the NA active site occurs upon binding peramivir in both the D197 and E197 NAs, this does not occur upon binding oseltamivir in the E197 NA. Lack of the E275 rotation would also account for the loss of slow binding and the partial resistance of influenza B wild type NAs to oseltamivir. Structural and Functional Basis of Resistance to Neuraminidase Inhibitors of Influenza B Viruses.,Oakley AJ, Barrett S, Peat TS, Newman J, Streltsov VA, Waddington L, Saito T, Tashiro M, McKimm-Breschkin JL J Med Chem. 2010 Aug 9. PMID:20695427[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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