View source for 5aaw


==Structure of a redesigned cross-reactive antibody to dengue virus with increased in vivo potency==
<StructureSection load='5aaw' size='340' side='right'caption='[[5aaw]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5aaw]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus Dengue virus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4udz 4udz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AAW 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]] 3.27&#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=5aaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aaw OCA], [https://pdbe.org/5aaw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aaw RCSB], [https://www.ebi.ac.uk/pdbsum/5aaw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aaw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6YFR6_9FLAV Q6YFR6_9FLAV] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dengue is the most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral responses may not be accessible by conventional B cell panning methods. To demonstrate an alternative strategy to generating a therapeutic antibody, we employed a non-immunodominant, but functionally relevant, epitope in domain III of the E protein, and engineered by structure-guided methods an antibody directed to it. The resulting antibody, Ab513, exhibits high-affinity binding to, and broadly neutralizes, multiple genotypes within all four serotypes. To assess therapeutic relevance of Ab513, activity against important human clinical features of dengue was investigated. Ab513 mitigates thrombocytopenia in a humanized mouse model, resolves vascular leakage, reduces viremia to nearly undetectable levels, and protects mice in a maternal transfer model of lethal antibody-mediated enhancement. The results demonstrate that Ab513 may reduce the public health burden from dengue.

Structure-Guided Design of an Anti-dengue Antibody Directed to a Non-immunodominant Epitope.,Robinson LN, Tharakaraman K, Rowley KJ, Costa VV, Chan KR, Wong YH, Ong LC, Tan HC, Koch T, Cain D, Kirloskar R, Viswanathan K, Liew CW, Tissire H, Ramakrishnan B, Myette JR, Babcock GJ, Sasisekharan V, Alonso S, Chen J, Lescar J, Shriver Z, Ooi EE, Sasisekharan R Cell. 2015 Jul 15. pii: S0092-8674(15)00827-2. doi: 10.1016/j.cell.2015.06.057. PMID:26189681<ref>PMID:26189681</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5aaw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dengue virus]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Lescar J]]
[[Category: Robinson L]]
[[Category: Sasisekharan R]]
[[Category: Wong Y]]