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6cfg
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the A/Vietnam/1203/2004 (H5N1) influenza virus hemagglutinin in complex with small molecule JNJ4796== | |
| + | <StructureSection load='6cfg' size='340' side='right'caption='[[6cfg]], [[Resolution|resolution]] 2.32Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6cfg]] is a 2 chain structure with sequence from [https://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=6CFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CFG 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]] 2.32Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EZ7:N-[2-(2-{4-[(R)-(2-methyl-2H-tetrazol-5-yl)(phenyl)methyl]piperazine-1-carbonyl}pyridin-4-yl)-1,3-benzoxazol-5-yl]acetamide'>EZ7</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6cfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cfg OCA], [https://pdbe.org/6cfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cfg RCSB], [https://www.ebi.ac.uk/pdbsum/6cfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cfg ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q5EP31_I04A1 Q5EP31_I04A1] 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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072] 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] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Recent characterization of broadly neutralizing antibodies (bnAbs) against influenza virus identified the conserved hemagglutinin (HA) stem as a target for development of universal vaccines and therapeutics. Although several stem bnAbs are being evaluated in clinical trials, antibodies are generally unsuited for oral delivery. Guided by structural knowledge of the interactions and mechanism of anti-stem bnAb CR6261, we selected and optimized small molecules that mimic the bnAb functionality. Our lead compound neutralizes influenza A group 1 viruses by inhibiting HA-mediated fusion in vitro, protects mice against lethal and sublethal influenza challenge after oral administration, and effectively neutralizes virus infection in reconstituted three-dimensional cell culture of fully differentiated human bronchial epithelial cells. Cocrystal structures with H1 and H5 HAs reveal that the lead compound recapitulates the bnAb hotspot interactions. | ||
| - | + | A small-molecule fusion inhibitor of influenza virus is orally active in mice.,van Dongen MJP, Kadam RU, Juraszek J, Lawson E, Brandenburg B, Schmitz F, Schepens WBG, Stoops B, van Diepen HA, Jongeneelen M, Tang C, Vermond J, van Eijgen-Obregoso Real A, Blokland S, Garg D, Yu W, Goutier W, Lanckacker E, Klap JM, Peeters DCG, Wu J, Buyck C, Jonckers THM, Roymans D, Roevens P, Vogels R, Koudstaal W, Friesen RHE, Raboisson P, Dhanak D, Goudsmit J, Wilson IA Science. 2019 Mar 8;363(6431). pii: 363/6431/eaar6221. doi:, 10.1126/science.aar6221. PMID:30846569<ref>PMID:30846569</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6cfg" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kadam RU]] | ||
| + | [[Category: Wilson IA]] | ||
Current revision
Crystal structure of the A/Vietnam/1203/2004 (H5N1) influenza virus hemagglutinin in complex with small molecule JNJ4796
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