1ce1
From Proteopedia
(New page: 200px<br /> <applet load="1ce1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ce1, resolution 1.9Å" /> '''1.9A STRUCTURE OF TH...) |
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| - | [[Image:1ce1.gif|left|200px]]<br /> | + | [[Image:1ce1.gif|left|200px]]<br /><applet load="1ce1" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1ce1, resolution 1.9Å" /> | caption="1ce1, resolution 1.9Å" /> | ||
'''1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN'''<br /> | '''1.9A STRUCTURE OF THE THERAPEUTIC ANTIBODY CAMPATH-1H FAB IN COMPLEX WITH A SYNTHETIC PEPTIDE ANTIGEN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | CAMPATH-1 antibodies have a long and successful history in the treatment | + | 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== | ==About this Structure== | ||
| - | 1CE1 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http:// | + | 1CE1 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CE1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bloomer, A | + | [[Category: Bloomer, A C.]] |
[[Category: Hale, G.]] | [[Category: Hale, G.]] | ||
| - | [[Category: James, L | + | [[Category: James, L C.]] |
[[Category: Waldmann, H.]] | [[Category: Waldmann, H.]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
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[[Category: therapeutic]] | [[Category: therapeutic]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:05:03 2008'' |
Revision as of 10:05, 21 February 2008
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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
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