View source for 6lyc


==Crystal structure of the NOD SIRPa complex with D4-2==
<StructureSection load='6lyc' size='340' side='right'caption='[[6lyc]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lyc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=6LYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LYC 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]] 1.36&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6lyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lyc OCA], [https://pdbe.org/6lyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lyc RCSB], [https://www.ebi.ac.uk/pdbsum/6lyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lyc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Medium-sized macrocyclic peptides are an alternative to small compounds and large biomolecules as a class of pharmaceutics. The CD47-SIRPalpha signaling axis functions as an innate immune checkpoint that inhibits phagocytosis in phagocytes and has been implicated as a promising target for cancer immunotherapy. The potential of macrocyclic peptides that target this signaling axis as immunotherapeutic agents has remained unknown, however. Here we have developed a macrocyclic peptide consisting of 15 amino acids that binds to the ectodomain of mouse SIRPalpha and efficiently blocks its interaction with CD47 in an allosteric manner. The peptide markedly promoted the phagocytosis of antibody-opsonized tumor cells by macrophages in vitro as well as enhanced the inhibitory effect of anti-CD20 or anti-gp75 antibodies on tumor formation or metastasis in vivo. Our results suggest that allosteric inhibition of the CD47-SIRPalpha interaction by macrocyclic peptides is a potential approach to cancer immunotherapy.

Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPalpha Interaction as a Potential Cancer Immunotherapy.,Hazama D, Yin Y, Murata Y, Matsuda M, Okamoto T, Tanaka D, Terasaka N, Zhao J, Sakamoto M, Kakuchi Y, Saito Y, Kotani T, Nishimura Y, Nakagawa A, Suga H, Matozaki T Cell Chem Biol. 2020 Sep 17;27(9):1181-1191.e7. doi:, 10.1016/j.chembiol.2020.06.008. Epub 2020 Jul 7. PMID:32640189<ref>PMID:32640189</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lyc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Matozaki T]]
[[Category: Matsuda M]]
[[Category: Murata Y]]
[[Category: Nakagawa A]]