1ce1
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ce1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ce1 OCA], [http://www.ebi.ac.uk/pdbsum/1ce1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ce1 RCSB]</span> | ||
}} | }} | ||
| Line 30: | Line 33: | ||
[[Category: therapeutic]] | [[Category: therapeutic]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:19:46 2008'' |
Revision as of 16:19, 30 March 2008
| |||||||
| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Sun Mar 30 19:19:46 2008
