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5t6n

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Revision as of 11:23, 16 September 2020

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin in complex with the antiviral drug arbidol

Structural highlights

5t6n is a 6 chain structure with sequence from I68a4 and I68a6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Gene:	HA (I68A4), HA (I68A6)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HEMA_I68A4] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity). [HEMA_I68A6] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.

Publication Abstract from PubMed

The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is approximately 16 A from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter- and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus.

Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol.,Kadam RU, Wilson IA Proc Natl Acad Sci U S A. 2016 Dec 21. pii: 201617020. doi:, 10.1073/pnas.1617020114. PMID:28003465^[1]

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

References

↑ Kadam RU, Wilson IA. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc Natl Acad Sci U S A. 2016 Dec 21. pii: 201617020. doi:, 10.1073/pnas.1617020114. PMID:28003465 doi:http://dx.doi.org/10.1073/pnas.1617020114

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5t6n"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin in complex with the antiviral drug arbidol==
-<StructureSection load='5t6n' size='340' side='right' caption='[[5t6n]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
+<StructureSection load='5t6n' size='340' side='right'caption='[[5t6n]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5t6n]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T6N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5t6n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/I68a4 I68a4] and [http://en.wikipedia.org/wiki/I68a6 I68a6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T6N FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=75U:ETHYL+6-BROMO-4-[(DIMETHYLAMINO)METHYL]-5-HYDROXY-1-METHYL-2-[(PHENYLSULFANYL)METHYL]-1H-INDOLE-3-CARBOXYLATE'>75U</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=75U:ETHYL+6-BROMO-4-[(DIMETHYLAMINO)METHYL]-5-HYDROXY-1-METHYL-2-[(PHENYLSULFANYL)METHYL]-1H-INDOLE-3-CARBOXYLATE'>75U</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></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=5t6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t6n OCA], [http://pdbe.org/5t6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t6n RCSB], [http://www.ebi.ac.uk/pdbsum/5t6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t6n ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=506350 I68A4]), HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6])</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=5t6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t6n OCA], [http://pdbe.org/5t6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t6n RCSB], [http://www.ebi.ac.uk/pdbsum/5t6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t6n ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5t6n" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: I68a4]]
+[[Category: I68a6]]
+[[Category: Large Structures]]
 [[Category: Kadam, R U]]
 [[Category: Wilson, I A]]

5t6n

From Proteopedia

Revision as of 11:23, 16 September 2020

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin in complex with the antiviral drug arbidol

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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