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| | {{STRUCTURE_1it9| PDB=1it9 | SCENE= }} | | {{STRUCTURE_1it9| PDB=1it9 | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF AN ANTIGEN-BINDING FRAGMENT FROM A HUMANIZED VERSION OF THE ANTI-HUMAN FAS ANTIBODY HFE7A'''
| + | ===CRYSTAL STRUCTURE OF AN ANTIGEN-BINDING FRAGMENT FROM A HUMANIZED VERSION OF THE ANTI-HUMAN FAS ANTIBODY HFE7A=== |
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| - | ==Overview==
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| - | Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays important roles in many biological processes, including the elimination of autoreactive lymphoid cells. We have previously obtained the mouse anti-Fas antibody HFE7A (m-HFE7A), which specifically induces apoptosis in inflammatory cells. In order to apply m-HFE7A for human therapy, we performed antibody humanization of m-HFE7A by grafting the mouse complementarity-determining regions (CDRs) to a human antibody. Five versions of humanized HFE7A (h-HFE7A) demonstrated the same antigen-binding affinity and same competition-binding activity against Fas as the chimeric HFE7A. Furthermore, these h-HFE7As induced the same degree of apoptosis in WR19L12a cells that express human Fas on their surface as chimeric HFE7A does. To further probe the structural basis for antibody humanization, we determined the three-dimensional structure of the h-HFE7A antigen-binding fragment (Fab) by X-ray crystallography and compared it with the crystal structure of the parent m-HFE7A Fab previously determined. The main-chain conformation in each h-HFE7A CDR is almost identical to that in m-HFE7A with root mean square (rms) deviations of 0.14-0.77 A. However, a significant segmental shift was observed in the CDR-L1 loop. Together with the high temperature factors of the CDR-L1 residues, both the loops are flexible, suggesting that the CDR-L1 loop would undergo conformational change upon binding to the antigen. Our results indicate that the humanization of m-HFE7A succeeded in maintaining the main-chain conformation as well as the flexibility of the CDR loop.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12499636}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12499636 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12499636}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Fab]] | | [[Category: Fab]] |
| | [[Category: Immunoglobulin]] | | [[Category: Immunoglobulin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:23:17 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 13:57:46 2008'' |
Revision as of 10:57, 1 July 2008
Template:STRUCTURE 1it9
CRYSTAL STRUCTURE OF AN ANTIGEN-BINDING FRAGMENT FROM A HUMANIZED VERSION OF THE ANTI-HUMAN FAS ANTIBODY HFE7A
Template:ABSTRACT PUBMED 12499636
About this Structure
Full crystallographic information is available from OCA.
Reference
Humanization of the mouse anti-Fas antibody HFE7A and crystal structure of the humanized HFE7A Fab fragment., Haruyama H, Ito S, Miyadai K, Takahashi T, Kawaida R, Takayama T, Hanzawa H, Hata T, Yamaguchi J, Yoshida-Kato H, Ichikawa K, Ohsumi J, Yonehara S, Serizawa N, Biol Pharm Bull. 2002 Dec;25(12):1537-45. PMID:12499636
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