3b7e: Difference between revisions
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==Neuraminidase of A/Brevig Mission/1/1918 H1N1 strain in complex with zanamivir== | ==Neuraminidase of A/Brevig Mission/1/1918 H1N1 strain in complex with zanamivir== | ||
<StructureSection load='3b7e' size='340' side='right' caption='[[3b7e]], [[Resolution|resolution]] 1.45Å' scene=''> | <StructureSection load='3b7e' size='340' side='right'caption='[[3b7e]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3b7e]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3b7e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. The May 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Influenza Neuraminidase'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_5 10.2210/rcsb_pdb/mom_2009_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B7E FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZMR:ZANAMIVIR'>ZMR</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=3b7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b7e OCA], [https://pdbe.org/3b7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b7e RCSB], [https://www.ebi.ac.uk/pdbsum/3b7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b7e ProSAT]</span></td></tr> | ||
< | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/NRAM_I18A0 NRAM_I18A0] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication (By similarity). Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Neuraminidase|Neuraminidase | *[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Influenza A virus]] | ||
[[Category: Influenza Neuraminidase]] | [[Category: Influenza Neuraminidase]] | ||
[[Category: Large Structures]] | |||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Wilson | [[Category: Wilson IA]] | ||
[[Category: Xu | [[Category: Xu X]] | ||
[[Category: Zhu | [[Category: Zhu X]] | ||
Latest revision as of 15:03, 30 August 2023
Neuraminidase of A/Brevig Mission/1/1918 H1N1 strain in complex with zanamivirNeuraminidase of A/Brevig Mission/1/1918 H1N1 strain in complex with zanamivir
Structural highlights
FunctionNRAM_I18A0 Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication (By similarity). Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious (By similarity). Publication Abstract from PubMedInfluenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 "Spanish flu" (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-A and 1.45-A resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147 to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza. Structural characterization of the 1918 influenza virus H1N1 neuraminidase.,Xu X, Zhu X, Dwek RA, Stevens J, Wilson IA J Virol. 2008 Nov;82(21):10493-501. Epub 2008 Aug 20. PMID:18715929[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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