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| | <StructureSection load='5l15' size='340' side='right'caption='[[5l15]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5l15' size='340' side='right'caption='[[5l15]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5l15]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/shanghai/02/2013(h7n9)) Influenza a virus (a/shanghai/02/2013(h7n9))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L15 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5L15 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5l15]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Shanghai/02/2013(H7N9)) Influenza A virus (A/Shanghai/02/2013(H7N9))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L15 FirstGlance]. <br> |
| - | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l14|5l14]], [[5l17|5l17]], [[5l18|5l18]]</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='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=1332244 Influenza A virus (A/Shanghai/02/2013(H7N9))])</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=5l15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l15 OCA], [https://pdbe.org/5l15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l15 RCSB], [https://www.ebi.ac.uk/pdbsum/5l15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l15 ProSAT]</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://proteopedia.org/fgij/fg.htm?mol=5l15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l15 OCA], [http://pdbe.org/5l15 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l15 RCSB], [http://www.ebi.ac.uk/pdbsum/5l15 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l15 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/R4NFR6_9INFA R4NFR6_9INFA]] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates.[RuleBase:RU361252] | + | [https://www.uniprot.org/uniprot/R4NFR6_9INFA R4NFR6_9INFA] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates.[RuleBase:RU361252] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Exo-alpha-sialidase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stevens, J]] | + | [[Category: Stevens J]] |
| - | [[Category: Yang, H]] | + | [[Category: Yang H]] |
| - | [[Category: H7n9]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Neuraminidase]]
| + | |
| Structural highlights
5l15 is a 1 chain structure with sequence from Influenza A virus (A/Shanghai/02/2013(H7N9)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
R4NFR6_9INFA Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates.[RuleBase:RU361252]
Publication Abstract from PubMed
Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir. The wild-type N9 crystal structure was determined in complex with oseltamivir, zanamivir, or sialic acid, and structural analysis was performed. Results: All substitutions conferred either reduced or highly reduced inhibition by at least 1 NA inhibitor; half of them caused reduced inhibition or highly reduced inhibition by all NA inhibitors. R292K conferred the highest increase in oseltamivir half-maximal inhibitory concentration (IC50), and E119D conferred the highest zanamivir IC50. Unlike N2 (another group 2NA), H274Y conferred highly reduced inhibition by oseltamivir. Additionally, R152K, a naturally occurring variation at the NA catalytic residue of A(H7N9) viruses, conferred reduced inhibition by laninamivir. Conclusions: The recNA method is a valuable tool for assessing the effect of NA changes on drug susceptibility of emerging influenza viruses.
Drug Susceptibility Evaluation of an Influenza A(H7N9) Virus by Analyzing Recombinant Neuraminidase Proteins.,Gubareva LV, Sleeman K, Guo Z, Yang H, Hodges E, Davis CT, Baranovich T, Stevens J J Infect Dis. 2017 Sep 15;216(suppl_4):S566-S574. doi: 10.1093/infdis/jiw625. PMID:28934455[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gubareva LV, Sleeman K, Guo Z, Yang H, Hodges E, Davis CT, Baranovich T, Stevens J. Drug Susceptibility Evaluation of an Influenza A(H7N9) Virus by Analyzing Recombinant Neuraminidase Proteins. J Infect Dis. 2017 Sep 15;216(suppl_4):S566-S574. doi: 10.1093/infdis/jiw625. PMID:28934455 doi:http://dx.doi.org/10.1093/infdis/jiw625
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