View source for 6xkr


==Structure of Sasanlimab Fab in complex with PD-1==
<StructureSection load='6xkr' size='340' side='right'caption='[[6xkr]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xkr]] is a 3 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=6XKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XKR 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]] 2.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6xkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkr OCA], [https://pdbe.org/6xkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xkr RCSB], [https://www.ebi.ac.uk/pdbsum/6xkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkr 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 ==
Development of antagonistic monoclonal antibodies that specifically target the immune checkpoint receptor, programmed cell death protein 1 (PD-1) is of great interest for cancer immunotherapy. Here we report the biophysical characteristics and non-clinical antagonistic activities of sasanlimab (PF-06801591), a humanized anti-PD-1 antibody of IgG4 isotype. We show that sasanlimab binds selectively and with similar high potency to human and cynomolgus monkey PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, with no detectable Fc-dependent effector function. The binding of sasanlimab to human and cynomolgus PD-1 is associated with the formation of a stable complex, which is likely to be the main driver of this high-affinity interaction. In vitro, sasanlimab significantly augmented T cell proliferation and cytokine production in mixed lymphocyte reaction and superantigen stimulation assays. In vivo, sasanlimab accelerated the incidence of graft versus host disease (GvHD) by enhancing T cell proliferation and cytokine secretion in a xenogeneic model of acute GvHD and halted the growth of MC-38 colon adenocarcinoma tumors in human PD-1 knock-in mice. Pharmacokinetic and toxicokinetic findings from cynomolgus monkey showed that sasanlimab was active and well-tolerated. Taken together, the data presented here support the clinical development of sasanlimab for the treatment of patients with advanced cancers as a single agent or in combination with other immunotherapies.

Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-Affinity Engineered Anti-Human PD-1 Antibody.,Al-Khami AA, Youssef S, Abdiche Y, Nguyen H, Chou J, Kimberlin CR, Chin SM, Kamperschroer C, Jessen B, Kern B, Budimir N, Dillon CP, Xu A, Clark JD, Chou J, Kraynov E, Rajpal A, Lin JC, Salek-Ardakani S Mol Cancer Ther. 2020 Aug 26. pii: 1535-7163.MCT-20-0093. doi:, 10.1158/1535-7163.MCT-20-0093. PMID:32847983<ref>PMID:32847983</ref>

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

==See Also==
*[[Cell death protein 3D structures|Cell death protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chin SM]]
[[Category: Kimberlin CR]]