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< | ==Crystal Structure of B/Perth Neuraminidase in complex with Peramivir== | ||
<StructureSection load='3k37' size='340' side='right'caption='[[3k37]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3k37]] is a 2 chain structure with sequence from [https://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=3K37 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K37 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCZ:3-(1-ACETYLAMINO-2-ETHYL-BUTYL)-4-GUANIDINO-2-HYDROXY-CYCLOPENTANECARBOXYLIC+ACID'>BCZ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=3k37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k37 OCA], [https://pdbe.org/3k37 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k37 RCSB], [https://www.ebi.ac.uk/pdbsum/3k37 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k37 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q3S340_9INFB Q3S340_9INFB] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We 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<ref>PMID:20695427</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3k37" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: McKimm-Breschkin JL]] | |||
[[Category: Oakley AJ]] | |||
== | |||
< | |||
[[Category: | |||
[[Category: McKimm-Breschkin | |||
[[Category: Oakley | |||
Latest revision as of 19:07, 1 November 2023
Crystal Structure of B/Perth Neuraminidase in complex with PeramivirCrystal Structure of B/Perth Neuraminidase in complex with Peramivir
Structural highlights
FunctionPublication 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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