1yzz
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1yc8|1YC8]], [[1yc7|1YC7]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yzz OCA], [http://www.ebi.ac.uk/pdbsum/1yzz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yzz RCSB]</span> | ||
}} | }} | ||
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[[Category: humanization]] | [[Category: humanization]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:27:01 2008'' |
Revision as of 22:27, 30 March 2008
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| , resolution 2.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Related: | 1YC8, 1YC7
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Humanized caban33 at room temperature
Overview
Heavy chain only antibodies of camelids bind their antigens with a single domain, the VHH, which acquired adaptations relative to classical VHs to function in the absence of a VL partner. Additional CDR loop conformations, outside the canonical loop structures of VHs, broaden the repertoire of the antigen-binding site. The combined effects of part of the CDR3 that folds over the "former" VL binding site and framework-2 mutations to more hydrophilic amino acids, enhance the solubility of VHH domains and prevent VL pairing. cAbAn33, a VHH domain specific for the carbohydrate moiety of the variant surface glycoprotein of trypanosomes, has a short CDR3 loop that does not cover the former VL binding site as well as a VH-specific Trp47 instead of the VHH-specific Gly47. Resurfacing its framework-2 region (mutations Tyr37Val, Glu44Gly and Arg45Leu) to mimic that of a human VH restores the VL binding capacity. In solution, the humanised VHH behaves as a soluble, monomeric entity, albeit with reduced thermodynamic stability and affinity for its antigen. Comparison of the crystal structures of cAbAn33 and its humanised derivative reveals steric hindrance exerted by VHH-specific residues Tyr37 and Arg45 that prevent the VL domain pairing, whereas Glu44 and Arg45 are key elements to avoid insolubility of the domain.
About this Structure
1YZZ is a Single protein structure of sequence from Camelus dromedarius. Full crystallographic information is available from OCA.
Reference
Antigen binding and solubility effects upon the veneering of a camel VHH in framework-2 to mimic a VH., Conrath K, Vincke C, Stijlemans B, Schymkowitz J, Decanniere K, Wyns L, Muyldermans S, Loris R, J Mol Biol. 2005 Jul 1;350(1):112-25. PMID:15913651
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