View source for 6vmz


==Crystal Structure of a H5N1 influenza virus hemagglutinin with CBS1117==
<StructureSection load='6vmz' size='340' side='right'caption='[[6vmz]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vmz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/chicken/Vietnam/30/2003(H5N1)) Influenza A virus (A/chicken/Vietnam/30/2003(H5N1))] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/chicken/Vietnam/4/2003(H5N1)) Influenza A virus (A/chicken/Vietnam/4/2003(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VMZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=R3P:2,6-bis(chloranyl)-~{N}-(1-propan-2-ylpiperidin-4-yl)benzamide'>R3P</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=6vmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vmz OCA], [https://pdbe.org/6vmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vmz RCSB], [https://www.ebi.ac.uk/pdbsum/6vmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vmz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q1KHK7_9INFA Q1KHK7_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.[RuleBase:RU003324]
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== Publication Abstract from PubMed ==
HA plays a critical role in influenza infection and, thus HA is a potential target for antivirals. Recently, our laboratories have described a novel fusion inhibitor, termed CBS1117, with EC(50) approximately 3 muM against group 1 HA. In this work, we characterize the binding properties of CBS1117 to avian H5 HA by x-ray crystallography, NMR, and mutagenesis. The x-ray structure of the complex shows that the compound binds near the HA fusion peptide, a region that plays a critical role in HA-mediated fusion. NMR studies demonstrate binding of CBS1117 to H5 HA in solution and show extensive hydrophobic contacts between the compound and HA surface. Mutagenesis studies further support the location of the compound binding site proximal to the HA fusion peptide and identify additional amino acids that are important to compound binding. Together, this work gives new insights into the CBS1117 mechanism of action and can be exploited to further optimize this compound and better understand the group specific activity of small-molecule inhibitors of HA-mediated entry.

Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor.,Antanasijevic A, Durst MA, Cheng H, Gaisina IN, Perez JT, Manicassamy B, Rong L, Lavie A, Caffrey M Life Sci Alliance. 2020 Jul 1;3(8):e202000724. doi: 10.26508/lsa.202000724. Print , 2020 Aug. PMID:32611549<ref>PMID:32611549</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6vmz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Antanasijevic A]]
[[Category: Caffrey M]]
[[Category: Durst MA]]
[[Category: Lavie A]]