7bxa: Difference between revisions
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The entry | ==Crystal structure of PD-1 in complex with tislelizumab Fab== | ||
<StructureSection load='7bxa' size='340' side='right'caption='[[7bxa]], [[Resolution|resolution]] 3.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7bxa]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BXA 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]] 3.32Å</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=7bxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bxa OCA], [https://pdbe.org/7bxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bxa RCSB], [https://www.ebi.ac.uk/pdbsum/7bxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bxa ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:[https://omim.org/entry/605218 605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:12402038</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.<ref>PMID:21276005</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front beta-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy. | |||
Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy.,Lee SH, Lee HT, Lim H, Kim Y, Park UB, Heo YS Biochem Biophys Res Commun. 2020 Jun 18;527(1):226-231. doi:, 10.1016/j.bbrc.2020.04.121. Epub 2020 May 1. PMID:32446372<ref>PMID:32446372</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7bxa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cell death protein 3D structures|Cell death protein 3D structures]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Heo YS]] | |||
[[Category: Kim YJ]] | |||
[[Category: Lee HT]] | |||
[[Category: Lee SH]] | |||
[[Category: Lim H]] | |||
[[Category: Park EB]] |