View source for 6hxw


==structure of human CD73 in complex with antibody IPH53==
<StructureSection load='6hxw' size='340' side='right'caption='[[6hxw]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hxw]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HXW 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]] 2.78&#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=ZN:ZINC+ION'>ZN</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=6hxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hxw OCA], [https://pdbe.org/6hxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hxw RCSB], [https://www.ebi.ac.uk/pdbsum/6hxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hxw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.<ref>PMID:21933152</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production of adenosine via the sequential activity of CD39 and CD73 ectoenzymes participates to the generation of an immunosuppressive tumor microenvironment. In order to disrupt the adenosine pathway, we generated two antibodies, IPH5201 and IPH5301, targeting human membrane-associated and soluble forms of CD39 and CD73, respectively, and efficiently blocking the hydrolysis of immunogenic ATP into immunosuppressive adenosine. These antibodies promoted antitumor immunity by stimulating dendritic cells and macrophages and by restoring the activation of T cells isolated from cancer patients. In a human CD39 knockin mouse preclinical model, IPH5201 increased the anti-tumor activity of the ATP-inducing chemotherapeutic drug oxaliplatin. These results support the use of anti-CD39 and anti-CD73 monoclonal antibodies and their combination with immune checkpoint inhibitors and chemotherapies in cancer.

Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies.,Perrot I, Michaud HA, Giraudon-Paoli M, Augier S, Docquier A, Gros L, Courtois R, Dejou C, Jecko D, Becquart O, Rispaud-Blanc H, Gauthier L, Rossi B, Chanteux S, Gourdin N, Amigues B, Roussel A, Bensussan A, Eliaou JF, Bastid J, Romagne F, Morel Y, Narni-Mancinelli E, Vivier E, Paturel C, Bonnefoy N Cell Rep. 2019 May 21;27(8):2411-2425.e9. doi: 10.1016/j.celrep.2019.04.091. PMID:31116985<ref>PMID:31116985</ref>

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

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Amigues B]]
[[Category: Roussel A]]