title: Exploring the cross-reactivity of S25-2: complex with a 5,6-dehydro-Kdo disaccharide.
abstract: The near-germline antibody S25-2 exhibits a remarkable cross-reactivity for oligosaccharides containing the bacterial lipopolysaccharide carbohydrate 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo). The recent synthesis of a variety of Kdo analogues permits a detailed structural analysis of the importance of specific interactions in antigen recognition by S25-2. The Kdo disaccharide analogue Kdo-(2→4)-5,6-dehydro-Kdo lacks a 5-OH group on the second Kdo residue and has been cocrystallized with S25-2. The structure reveals that the modification of the Kdo residue at position 5 results in a rearrangement of intramolecular hydrogen bonds in the antigen that allows it to assume a novel conformation in the antibody-combining site. The cross-reactive binding of S25-2 to this synthetic ligand highlights the adaptability of this antibody to non-natural synthetic analogues.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC V8W 3P6, Canada. cbrooks1@ualberta.ca
authors.forename: Cory L
authors.initials: CL
authors.lastname: Brooks
authors.forename: Kurt
authors.initials: K
authors.lastname: Wimmer
authors.forename: Paul
authors.initials: P
authors.lastname: Kosma
authors.forename: Sven
authors.initials: S
authors.lastname: Müller-Loennies
authors.forename: Lore
authors.initials: L
authors.lastname: Brade
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Evans
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody / Q000276:immunology; D002236:Carbohydrate Conformation; D003429:Cross Reactions; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D013400:Sugar Acids / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D013400:Sugar Acids; C120356:3-deoxy-manno-oct-2-ulopyranosonic acid