1ce1
From Proteopedia
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'''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''' | ||
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[[Category: James, L C.]] | [[Category: James, L C.]] | ||
[[Category: Waldmann, H.]] | [[Category: Waldmann, H.]] | ||
| - | [[Category: | + | [[Category: Antibody]] |
| - | [[Category: | + | [[Category: Cd52]] |
| - | [[Category: | + | [[Category: Therapeutic]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:37:27 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 09:37, 2 May 2008
1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN
Overview
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.
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 Page seeded by OCA on Fri May 2 12:37:27 2008
