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PDBsum entry 1fn4
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Immune system
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PDB id
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1fn4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of FAB198, An efficient protector of the acetylcholine receptor against myasthenogenic antibodies.
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Authors
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K.Poulas,
E.Eliopoulos,
E.Vatzaki,
J.Navaza,
M.Kontou,
N.Oikonomakos,
K.R.Acharya,
S.J.Tzartos.
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Ref.
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Eur J Biochem, 2001,
268,
3685-3693.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the Fab fragment of the rat monoclonal antibody 198,
with protective activity for the main immunogenic region of the human muscle
acetylcholine receptor against the destructive action of myasthenic antibodies,
has been determined and refined to 2.8 A resolution by X-ray crystallographic
methods. The mouse anti-lysozyme Fab D1.3 was used as a search model in
molecular replacement with the AMORE software. The complementarity determining
regions (CDR)-L2, CDR-H1 and CDR-H2 belong to canonical groups. Loops CDR-L3,
CDR-H2 and CDR-H3, which seem to make a major contribution to binding, were
analyzed and residues of potential importance for antigen-binding are examined.
The antigen-binding site was found to be a long crescent-shaped crevice. The
structure should serve as a model in the rational design of very high affinity
humanized mutants of Fab198, appropriate for therapeutic approaches in the model
autoimmune disease myasthenia gravis.
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Figure 1.
Fig. 1. Ribbon representation of the Fab198 molecule. The
molecule exhibits the typical immunoglobulin fold. The CDRs are
shown in bold. (A) The molecule is shown with the variable
chains (V[L]–V[H]) at the top and the constant (C[L]–C[H])
at the bottom. (B) View from the top of the molecule showing the
access to the binding crevice (as in Fig. 5 Go- ). The
figure was prepared with MOLSCRIPT [41].
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Figure 5.
Fig. 5. Top view of the antigen-binding site of the Fab198
molecule in stereo. The binding crevice is formed by residues of
V[H] (in red) and V[L] (in blue). The important interacting
residues are labeled in their respective colours. Black lines
represent the Ca trace of VH and VL. CDRs (Ca atoms only) are
represented by thick black lines and labeled (L1-L3, H1-H3).
This view corresponds to Fig. 1B Go-and Fig.
6B Go-. The
drawing was prepared with MOLSCRIPT [41].
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
Eur J Biochem
(2001,
268,
3685-3693)
copyright 2001.
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