Evidence for the extended helical nature of polysaccharide epitopes. The 2.8 A resolution structure and thermodynamics of ligand binding of an antigen binding fragment specific for alpha-(2-->8)-polysialic acid: Biochemistry

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TypeArticle
Journal titleBiochemistry
Volume34
Issue20
Pages67376744; # of pages: 8
SubjectACID; ACID RESIDUES; Acids; Antibodies; Antibodies,Monoclonal; antibody; ANTIGEN; binding; Binding Sites; Binding Sites,Antibody; BINDING-SITE; Canada; chemistry; conformation; CONFORMATIONAL; crystal; Crystallization; Crystallography,X-Ray; Diffusion; DISTRIBUTION; epitope; Epitopes; EQUILIBRIUM; Haptens; Immunoglobulin G; IMMUNOGLOBULIN-G; Immunoglobulins; Immunoglobulins,Fab; immunology; LIGAND; ligand binding; Macromolecular Systems; metabolism; method; Methods; MODEL; Models,Molecular; MOLECULAR; MONOCLONAL-ANTIBODIES; MONOCLONAL-ANTIBODY; oligosaccharide; Oligosaccharides; peptide; Peptide Fragments; Polymers; POLYSACCHARIDE; Protein Structure,Secondary; R-FACTOR; RESIDUES; RESOLUTION; SIALIC; Sialic Acids; SIALIC-ACID; SITE; SITES; solution; Solutions; SPECIFICITY; structure; SYSTEM; SYSTEMS; Thermodynamics; X-ray
AbstractThe antigen binding fragment from an IgG2a kappa murine monoclonal antibody with specificity for alpha-(2-->8)-linked sialic acid polymers has been prepared and crystallized in the absence of hapten. Crystals were grown by vapor diffusion equilibrium with 16-18% polyethylene glycol 4000 solutions. The structure was solved by molecular replacement methods and refined to a conventional R factor of 0.164 for data to 2.8 A. The binding site is observed to display a shape and distribution of charges that is complementary to that of the predicted conformation of the oligosaccharide epitope. A thermodynamic description of ligand binding has been compiled for oligosaccharides ranging in length from 9 to 41 residues, and the data for the largest ligand has been used in a novel way to estimate the size of the antigen binding site. A model of antigen binding is presented that satisfies this thermodynamic data, as well as a previously reported requirement of conformational specificity of the oligosaccharide. X-ray crystallographic and thermodynamic evidence are consistent with a binding site that accommodates at least eight sialic acid residues
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberEVANS1995
NPARC number9371205
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Record identifier1df6fea1-59aa-4dbc-90d2-3463988cd415
Record created2009-07-10
Record modified2016-05-09
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