1ce1

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1ce1, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 Nov 18 09:27:25 2007