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6cf5

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Revision as of 09:37, 18 December 2019

Crystal structure of the A/Viet Nam/1203/2004(H5N1) influenza virus hemagglutinin in complex with small molecule N-Cyclohexyltaurine

Structural highlights

6cf5 is a 6 chain structure with sequence from Influenza a virus (a/viet nam/1203/2004(h5n1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	HA (Influenza A virus (A/Viet Nam/1203/2004(H5N1)))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[Q5EP31_9INFA] 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).[RuleBase:RU003324][SAAS:SAAS008980_004_327643] [HEMA_I02A6] 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 influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N-cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-A and 2.57-A resolution, respectively, revealed that N-cyclohexyltaurine binds to the heart of the conserved HA RBS. N-cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-pi interactions with the HA. In H3/HK68, N-cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.

A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin.,Kadam RU, Wilson IA Proc Natl Acad Sci U S A. 2018 Apr 2. pii: 1801999115. doi:, 10.1073/pnas.1801999115. PMID:29610325^[1]

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

References

↑ Kadam RU, Wilson IA. A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin. Proc Natl Acad Sci U S A. 2018 Apr 2. pii: 1801999115. doi:, 10.1073/pnas.1801999115. PMID:29610325 doi:http://dx.doi.org/10.1073/pnas.1801999115

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/6cf5"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the A/Viet Nam/1203/2004(H5N1) influenza virus hemagglutinin in complex with small molecule N-Cyclohexyltaurine==
-<StructureSection load='6cf5' size='340' side='right' caption='[[6cf5]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
+<StructureSection load='6cf5' size='340' side='right'caption='[[6cf5]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6cf5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/viet_nam/1203/2004(h5n1)) Influenza a virus (a/viet nam/1203/2004(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CF5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CF5 FirstGlance]. <br>
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[Hemagglutinin|Hemagglutinin]]
+*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Kadam, R U]]
 [[Category: Wilson, I A]]

6cf5

From Proteopedia

Revision as of 09:37, 18 December 2019

Crystal structure of the A/Viet Nam/1203/2004(H5N1) influenza virus hemagglutinin in complex with small molecule N-Cyclohexyltaurine

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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