View source for 4wyj


==Adenovirus 3 head domain mutant V239D==
<StructureSection load='4wyj' size='340' side='right'caption='[[4wyj]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wyj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_B3 Human adenovirus B3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WYJ 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4wyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyj OCA], [https://pdbe.org/4wyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wyj RCSB], [https://www.ebi.ac.uk/pdbsum/4wyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIKE_ADE03 SPIKE_ADE03] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A central treatment resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. We have developed a small recombinant protein (JO-1) that triggers the transient opening of intercellular junctions and thus increases the efficacy of monoclonal antibodies and chemotherapeutic drugs without causing toxicity in mouse tumor models. Here, we provide data toward the clinical translation of an affinity-enhanced version of JO-1, which we call JO-4, in combination with PEGylated liposomal doxorubicin (PLD)/Doxil for ovarian cancer therapy. We have presented X-ray crystallography data suggesting a structural basis for the higher affinity of JO-4 to DSG2. We also confirmed JO-4 efficacy in a xenograft model with primary ovarian cancer cells showing that JO-4 can salvage Doxil therapy when given at a dose that was threefold lower than the therapeutic dose. Furthermore, we tested the safety of intravenous JO-4 alone and in combination with Doxil in Macaca fascicularis, an adequate animal model for predicting toxicity in humans. Our studies did not show critical JO-4-related toxicity or an increase of Doxil-related side effects. Our efficacy and safety data will help to support an Investigational new drug-filing for a JO-4/Doxil combination treatment.

Preclinical safety and efficacy studies with an affinity-enhanced epithelial junction opener and PEGylated liposomal doxorubicin.,Richter M, Yumul R, Wang H, Saydaminova K, Ho M, May D, Baldessari A, Gough M, Drescher C, Urban N, Roffler S, Zubieta C, Carter D, Fender P, Lieber A Mol Ther Methods Clin Dev. 2015 Mar 11;2:15005. doi: 10.1038/mtm.2015.5., eCollection 2015. PMID:26029716<ref>PMID:26029716</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wyj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human adenovirus B3]]
[[Category: Large Structures]]
[[Category: Fender P]]
[[Category: Lieber A]]
[[Category: Zubieta C]]