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| [[Image:1yzz.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1yzz| PDB=1yzz | SCENE= }} | | {{STRUCTURE_1yzz| PDB=1yzz | SCENE= }} |
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| '''Humanized caban33 at room temperature'''
| | ===Humanized caban33 at room temperature=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15913651}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15913651 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15913651}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Camel antibody]] | | [[Category: Camel antibody]] |
| [[Category: Humanization]] | | [[Category: Humanization]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:01:09 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:25:52 2008'' |
