5f3b: Difference between revisions

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'''Unreleased structure'''


The entry 5f3b is ON HOLD  until Paper Publication
==Structure of myostatin in complex with chimeric RK35 antibody==
<StructureSection load='5f3b' size='340' side='right'caption='[[5f3b]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5f3b]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F3B 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]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5f3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f3b OCA], [https://pdbe.org/5f3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f3b RCSB], [https://www.ebi.ac.uk/pdbsum/5f3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f3b ProSAT]</span></td></tr>
</table>
== Disease ==
[https://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 ==
[https://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.


Authors: Parris, K.D., Mosyak, L.
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>


Description: Structure of myostatin in complex with chimeric RK35 antibody
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Mosyak, L]]
<div class="pdbe-citations 5f3b" style="background-color:#fffaf0;"></div>
[[Category: Parris, K.D]]
 
==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Growth differentiation factor 3D STRUCTURES|Growth differentiation factor 3D STRUCTURES]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mosyak L]]
[[Category: Parris KD]]
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