Recognition of a Cell-Surface Oligosaccharide of Pathogenic Salmonella by an Antibody Fab Fragment

• Published in: Science (American Association for the Advancement of Science) Vol. 253; no. 5018; pp. 442 - 445
• Main Authors: Cygler, Miroslaw, Rose, David R., Bundle, David R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 26.07.1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Antibodies; Antigen-Antibody Complex; Antigen-antibody reactions, antigen-antibody complexes, antibody-complement and others. Study of affinity. Antigen presentation; Antigens; Atoms; Biological and medical sciences; Carbohydrate Conformation; Carbohydrate Sequence; Carbohydrates; Crystal structure; Epitopes; Epitopes - chemistry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hydrogen bonds; Immune complexes; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - immunology; Immunoglobulin G - classification; Immunoglobulin G - immunology; Lipopolysaccharides - chemistry; Lipopolysaccharides - immunology; Models, Molecular; Molecular immunology; Molecular Sequence Data; Molecular structure; Molecules; Oligosaccharides; Oligosaccharides - chemistry; Oligosaccharides - immunology; Protein Conformation; Salmonella - immunology; Salmonella - pathogenicity; Science; Sugars; X-ray crystallography; Salmonella; Oligosaccharide; Antigen antibody reaction; Hypervariable region; IgG1; Monoclonal antibody; Fab-Fragment; X ray diffraction; Cell surface; O antigen; Bacteria; Molecular complex; Enterobacteriaceae; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1713710

The 2.05 angstrom (Å) resolution crystal structure of a dodecasaccharide-Fab complex revealed an unusual carbohydrate recognition site, defined by aromatic amino acids and a structured water molecule, rather than the carboxylic acid and amide side chains that are features of transport and other, carbohydrate binding proteins. A trisaccharide epitope of a branched bacterial lipopolysaccharide fills this hydrophobic pocket (8 Å deep by 7 Å wide) in an entropy-assisted association (association constant = 2.05 × 10$^5$ liters per mole, enthalpy = -20.5 ± 1.7 kilojoules per mole, and temperature times entropy = + 10.0 ± 2.9 kilojoules per mole). The requirement for the complementarity of van der Waals surfaces and the requirements of saccharide-saccharide and protein-saccharide hydrogen-bonding networks determine~ the antigen conformation adopted in the bound state