View source for 6jht


==The cryo-EM structure of HAV bound to a neutralizing antibody-F9==
<StructureSection load='6jht' size='340' side='right'caption='[[6jht]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jht]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_hepatitis_A_virus_Hu/Australia/HM175/1976 Human hepatitis A virus Hu/Australia/HM175/1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JHT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.79&#8491;</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=6jht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jht OCA], [https://pdbe.org/6jht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jht RCSB], [https://www.ebi.ac.uk/pdbsum/6jht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jht ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are still required, especially during fulminant hepatitis outbreaks. A more in-depth understanding of the antigenic characteristics of HAV and the mechanisms of neutralization could aid in the development of rationally designed antiviral drugs targeting HAV. In this paper, 4 new antibodies-F4, F6, F7, and F9-are reported that potently neutralize HAV at 50% neutralizing concentration values (neut50) ranging from 0.1 nM to 0.85 nM. High-resolution cryo-electron microscopy (cryo-EM) structures of HAV bound to F4, F6, F7, and F9, together with results of our previous studies on R10 fragment of antigen binding (Fab)-HAV complex, shed light on the locations and nature of the epitopes recognized by the 5 neutralizing monoclonal antibodies (NAbs). All the epitopes locate within the same patch and are highly conserved. The key structure-activity correlates based on the antigenic sites have been established. Based on the structural data of the single conserved antigenic site and key structure-activity correlates, one promising drug candidate named golvatinib was identified by in silico docking studies. Cell-based antiviral assays confirmed that golvatinib is capable of blocking HAV infection effectively with a 50% inhibitory concentration (IC50) of approximately 1 muM. These results suggest that the single conserved antigenic site from complete HAV capsid is a good antiviral target and that golvatinib could function as a lead compound for anti-HAV drug development.

Structural basis for neutralization of hepatitis A virus informs a rational design of highly potent inhibitors.,Cao L, Liu P, Yang P, Gao Q, Li H, Sun Y, Zhu L, Lin J, Su D, Rao Z, Wang X PLoS Biol. 2019 Apr 30;17(4):e3000229. doi: 10.1371/journal.pbio.3000229., eCollection 2019 Apr. PMID:31039149<ref>PMID:31039149</ref>

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

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human hepatitis A virus Hu/Australia/HM175/1976]]
[[Category: Large Structures]]
[[Category: Cao L]]
[[Category: Gao Q]]
[[Category: Li H]]
[[Category: Lin J]]
[[Category: Liu P]]
[[Category: Rao Z]]
[[Category: Su D]]
[[Category: Sun Y]]
[[Category: Wang X]]
[[Category: Yang P]]
[[Category: Zhu L]]