Crystallographic analysis of the interaction between cyclosporin A and the Fab fragment of a monoclonal antibody.
The structure of the complex between cyclosporin A and the Fab fragment of a monoclonal antibody has been established by crystallographic analysis to 2.65 A resolution. The structure has been solved by molecular replacement using a composite Fab model. The current R-factor after refinement is 0.179 between 8 and 2.65 A resolution. The antibody is one among three known structures with long H3 loops. This loop conformation is observed for the first time in the presence of the antigen. Residues from all six hypervariable loops interact with cyclosporin A. However, the 17 residues long loop H3 is the main contributor to the buried combining site area and to the van der Waals contacts made with cyclosporin A, with 52 and 63%, respectively, of the total contribution.
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UPR de Biologie Structurale, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
Rees
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Thierry
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JC
Altschuh
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D
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D003198:Computer Simulation; D003461:Crystallography; D016572:Cyclosporine / Q000737:chemistry* / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D016572:Cyclosporine