View source for 6lun


==NN2101 Antibody Fab fragment==
<StructureSection load='6lun' size='340' side='right'caption='[[6lun]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lun]] is a 4 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=6LUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LUN 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]] 1.9&#8491;</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=6lun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lun OCA], [https://pdbe.org/6lun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lun RCSB], [https://www.ebi.ac.uk/pdbsum/6lun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lun ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CD117/c-kit, a tyrosine kinase receptor, plays a critical role in hematopoiesis, pigmentation, and fertility. The overexpression and activation of c-kit are thought to promote tumor growth and have been reported in various cancers, including leukemia, glioblastoma and mastocytosis. To disrupt the SCF/c-kit signaling axis in cancer, we generated a c-kit antagonist human antibody (NN2101) that binds to domain 2/3 of c-kit. This completely blocked the SCF-mediated phosphorylation of c-kit and inhibited TF-1 cell proliferation, erythroleukemia. In addition, the examination of binding affinity using surface plasmon resonance (SPR) assay showed that NN2101 can bind to c-kit of monkeys (K(D) = 2.92 x 10(-10) M), rats (K(D) = 1.68 x 10(-6) M), mice (K(D) = 11.5 x 10(-9) M), and humans (K(D) = 2.83 x 10(-12) M). We showed that NN2101 does not cause antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The immunogenicity of NN2101 was similar to that of bevacizumab. Furthermore, the crystal structure of NN2101 Fab was determined and the structure of NN2101 Fab:c-kit complex was modeled. Structural information, as well as mutagenesis results, revealed that NN2101 can bind to the SCF-binding regions of c-kit. Collectively, we generated a c-kit neutralizing human antibody (NN2101) for the treatment of erythroleukemia and characterized its biophysical properties. NN2101 can potentially be used as a therapeutic antibody to treat different cancers.

Development and characterization of a fully human antibody targeting SCF/c-kit signaling.,Kim JO, Kim HN, Kim KH, Baek EJ, Park JY, Ha K, Heo DR, Seo MD, Park SG Int J Biol Macromol. 2020 Sep 15;159:66-78. doi: 10.1016/j.ijbiomac.2020.05.045. , Epub 2020 May 11. PMID:32437800<ref>PMID:32437800</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lun" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kim HN]]
[[Category: Park SK]]
[[Category: Seo MD]]