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6u02

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Revision as of 13:19, 25 December 2019

CryoEM-derived model of NA-63 Fab in complex with N9 Shanghai2

Structural highlights

6u02 is a 12 chain structure with sequence from Human and Influenza a virus (a/environment/shanghai/s1439/2013(h7n9)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	NA (Influenza A virus (A/environment/Shanghai/S1439/2013(H7N9)))
Activity:	Exo-alpha-sialidase, with EC number 3.2.1.18
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[S5MF06_9INFA] 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.[HAMAP-Rule:MF_04071][SAAS:SAAS00844152]

Publication Abstract from PubMed

Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host protection. However, our understanding of the nature and range of target epitopes is limited because of a lack of human antibody structures with influenza neuraminidase. Here, we describe crystal and cryogenic electron microscopy (cryo-EM) structures of NAs from human-infecting avian H7N9 viruses in complex with five human anti-N9 antibodies, systematically defining several antigenic sites and antibody epitope footprints. These antibodies either fully or partially block the NA active site or bind to epitopes distant from the active site while still showing neuraminidase inhibition. The inhibition of antibodies to NAs was further analyzed by glycan array and solution-based NA activity assays. Together, these structural studies provide insights into protection by anti-NA antibodies and templates for the development of NA-based influenza virus vaccines and therapeutics.

Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies.,Zhu X, Turner HL, Lang S, McBride R, Bangaru S, Gilchuk IM, Yu W, Paulson JC, Crowe JE Jr, Ward AB, Wilson IA Cell Host Microbe. 2019 Oct 24. pii: S1931-3128(19)30526-8. doi:, 10.1016/j.chom.2019.10.002. PMID:31757767^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhu X, Turner HL, Lang S, McBride R, Bangaru S, Gilchuk IM, Yu W, Paulson JC, Crowe JE Jr, Ward AB, Wilson IA. Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies. Cell Host Microbe. 2019 Oct 24. pii: S1931-3128(19)30526-8. doi:, 10.1016/j.chom.2019.10.002. PMID:31757767 doi:http://dx.doi.org/10.1016/j.chom.2019.10.002

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6u02"

@@ Line 3: / Line 3: @@
 <StructureSection load='6u02' size='340' side='right'caption='[[6u02]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6u02]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U02 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6u02]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/environment/shanghai/s1439/2013(h7n9)) Influenza a virus (a/environment/shanghai/s1439/2013(h7n9))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U02 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=1347105 Influenza A virus (A/environment/Shanghai/S1439/2013(H7N9))])</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=6u02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u02 OCA], [http://pdbe.org/6u02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u02 RCSB], [http://www.ebi.ac.uk/pdbsum/6u02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u02 ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Exo-alpha-sialidase]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Turner, H L]]

6u02

From Proteopedia

Revision as of 13:19, 25 December 2019

CryoEM-derived model of NA-63 Fab in complex with N9 Shanghai2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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