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[[Image:1ce1.gif|left|200px]]
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{{STRUCTURE_1ce1|  PDB=1ce1  |  SCENE=  }}  
{{STRUCTURE_1ce1|  PDB=1ce1  |  SCENE=  }}  


'''1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN'''
===1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN===




==Overview==
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CAMPATH-1 antibodies have a long and successful history in the treatment of leukaemia, autoimmune disease and transplant rejection. The first antibody to undergo "humanisation", CAMPATH-1H, permits treatment with limited patient anti-globulin response. It recognises the CD52 antigen which is a small glycosylphosphatidylinositol(GPI)-anchored protein expressed on lymphocytes and mediates cell depletion. We present the 1.9 A structure of the CAMPATH-1H Fab complexed [corrected] with an analogue of the antigenic determinant of CD52. Analysis of the CAMPATH-1H binding site reveals that in contrast to most antibodies CDR L3 plays a dominant role in antigen binding. Furthermore CDR H3, which is essential for effective antigen recognition in most antibodies, participates in only two main-chain interactions in CAMPATH-1H. The CAMPATH-1H binding site is highly basic; ionic interaction with the enthanolamine phosphate of the CD52 GPI anchor has long been hypothesised to be important in antigen binding. The structure reveals a number of important specific ionic interactions, including Lys53H but not Lys52bH as had previously been suggested. Prolonged treatment with CAMPATH-1H can lead to patient anti-idiotype responses which may be exacerbated by the unusually high number of basic residues in the antibody. This suggests that a strategy where redundant basic residues are replaced with neutral counterparts may be effective in further reducing the immunogenicity of this versatile and widely used antibody.
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==About this Structure==
==About this Structure==
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[[Category: Cd52]]
[[Category: Cd52]]
[[Category: Therapeutic]]
[[Category: Therapeutic]]
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Revision as of 17:36, 30 June 2008

File:1ce1.png

Template:STRUCTURE 1ce1

1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN

Template:ABSTRACT PUBMED 10366506

About this Structure

1CE1 is a Protein complex structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.

Reference

1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen., James LC, Hale G, Waldmann H, Bloomer AC, J Mol Biol. 1999 Jun 4;289(2):293-301. PMID:10366506

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