5f3h: Difference between revisions
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The entry | ==Structure of myostatin in complex with humanized RK35 antibody== | ||
<StructureSection load='5f3h' size='340' side='right' caption='[[5f3h]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5f3h]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F3H FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f3b|5f3b]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5f3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f3h OCA], [http://pdbe.org/5f3h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f3h RCSB], [http://www.ebi.ac.uk/pdbsum/5f3h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f3h ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN]] Myostatin-related muscle hypertrophy. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN]] Acts specifically as a negative regulator of skeletal muscle growth. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the co-crystal structures of myostatin with the chimeric (Protein Databank (PDB) id 5F3B) and CDR-grafted anti-myostatin antibody (PDB id 5F3H), allowing us to computationally predict the structurally important CDR residues as well as those making significant contacts with the antigen. Structure-based rational design enabled further germlining of the CDR-grafted antibody, reducing the murine content of the antibody without affecting antigen binding. The overall "humanness" was increased for both the light and heavy chain variable regions. | |||
Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody.,Apgar JR, Mader M, Agostinelli R, Benard S, Bialek P, Johnson M, Gao Y, Krebs M, Owens J, Parris K, St Andre M, Svenson K, Morris C, Tchistiakova L MAbs. 2016 Oct;8(7):1302-1318. Epub 2016 Sep 13. PMID:27625211<ref>PMID:27625211</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5f3h" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Mosyak, L]] | [[Category: Mosyak, L]] | ||
[[Category: Parris, K | [[Category: Parris, K D]] | ||
[[Category: Antibody]] | |||
[[Category: Complex]] | |||
[[Category: Myostatin]] | |||
[[Category: Signaling protein-immune system complex]] | |||
