6hxw

structure of human CD73 in complex with antibody IPH53

spinqualitylabelsall models 6hxw, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hxw is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.78Å Ligands: NAG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease 5NTD_HUMAN Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function 5NTD_HUMAN Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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