View source for 6osv


==Potent and Selective Antitumor Antibody Targeting a Membrane-Proximal Epitope of ROR2==
<StructureSection load='6osv' size='340' side='right'caption='[[6osv]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6osv]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OSV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OSV FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROR2, NTRKR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6osv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6osv OCA], [http://pdbe.org/6osv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6osv RCSB], [http://www.ebi.ac.uk/pdbsum/6osv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6osv ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN]] Autosomal recessive Robinow syndrome;Brachydactyly type B. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. 
== Function ==
[[http://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN]] Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation.<ref>PMID:17717073</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues, but is up-regulated in a diverse set of hematologic and solid malignancies. Thus, ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning, and again co-crystallized with hROR2-Kr. We show that the affinity matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T-cell engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Affinity maturation, humanization, and co-crystallization of a rabbit anti-human ROR2 monoclonal antibody for therapeutic applications.,Goydel RS, Weber J, Peng H, Qi J, Soden J, Freeth J, Park H, Rader C J Biol Chem. 2020 Mar 19. pii: RA120.012791. doi: 10.1074/jbc.RA120.012791. PMID:32193207<ref>PMID:32193207</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6osv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: European rabbit]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Park, H]]
[[Category: Rader, C]]
[[Category: Antibody]]
[[Category: Immune system]]
[[Category: Immune sytem-transferase complex]]
[[Category: Kringle domain]]
[[Category: Phage display]]
[[Category: Receptor tyrosine kinase-like orphan receptor]]
[[Category: Ror2]]
[[Category: Scfv]]
[[Category: Single chain fv]]