5b8c: Difference between revisions
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==High resolution structure of the human PD-1 in complex with pembrolizumab Fv== | |||
<StructureSection load='5b8c' size='340' side='right'caption='[[5b8c]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5b8c]] is a 12 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=5B8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B8C 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]] 2.146Å</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=5b8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b8c OCA], [https://pdbe.org/5b8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b8c RCSB], [https://www.ebi.ac.uk/pdbsum/5b8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b8c ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1ECD) was reported at a resolution of 2.9 A. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target. Here, we present the independently determined crystal structure of the Fv fragment of pembrolizumab (PemFv) in complex with the PD-1ECD at a resolution of 2.15 A. This high-resolution structure allows the accurate mapping of the interaction including water-mediated hydrogen bonds and provides, for the first time, a coherent explanation of PD-1 antagonism by pembrolizumab. Our structural data also provides new insights into the rational design of improved anti-PD-1 therapeutics. | |||
High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1.,Horita S, Nomura Y, Sato Y, Shimamura T, Iwata S, Nomura N Sci Rep. 2016 Oct 13;6:35297. doi: 10.1038/srep35297. PMID:27734966<ref>PMID:27734966</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5b8c" 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: Horita S]] | |||
[[Category: Iwata S]] | |||
[[Category: Nomura N]] | |||
[[Category: Shimamura T]] | |||
Latest revision as of 06:52, 21 November 2024
High resolution structure of the human PD-1 in complex with pembrolizumab FvHigh resolution structure of the human PD-1 in complex with pembrolizumab Fv
Structural highlights
Publication Abstract from PubMedPembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1ECD) was reported at a resolution of 2.9 A. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target. Here, we present the independently determined crystal structure of the Fv fragment of pembrolizumab (PemFv) in complex with the PD-1ECD at a resolution of 2.15 A. This high-resolution structure allows the accurate mapping of the interaction including water-mediated hydrogen bonds and provides, for the first time, a coherent explanation of PD-1 antagonism by pembrolizumab. Our structural data also provides new insights into the rational design of improved anti-PD-1 therapeutics. High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1.,Horita S, Nomura Y, Sato Y, Shimamura T, Iwata S, Nomura N Sci Rep. 2016 Oct 13;6:35297. doi: 10.1038/srep35297. PMID:27734966[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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