1m71
Crystal structure of a Monoclonal Fab Specific for Shigella Flexneri Y lipopolysaccharide
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OverviewOverview
The antigenic recognition of Shigella flexneri O-polysaccharide, which, consists of a repeating unit ABCD, [-->2)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-beta, -D-GlcpNAc-(1-->], by the monoclonal antibody SYA/J6 (IgG3, kappa) has, been investigated by crystallographic analysis of the Fab domain and its, two complexes with two antigen segments (a pentasaccharide Rha A-Rha B-Rha, C-GlcNAc D-Rha A' and a modified trisaccharide Rha B-Rha C-GlcNAc D in, which Rha C* is missing a C2-OH group). These complex structures, the, first for a Fab specific for a periodic linear heteropolysaccharide, reveal a binding site groove (between the V(H) and V(L) domains) that, makes polar and nonpolar contacts with all the sugar residues of the, pentasaccharide. Both main-chain and side-chain atoms of the Fab are used, in ligand binding. The charged side chain of Glu H50 of CDR H2 forms, crucial hydrogen bonds to GlcNAc of the oligosaccharides. The modified, trisaccharide is more buried and fits more snugly than the, pentasaccharide. It also makes as many contacts (approximately 75) with, the Fab as the pentasaccharide, including the same number of hydrogen, bonds (eight, with four being identical). It is further engaged in more, hydrophobic interactions than the pentasaccharide. These three features, favorable to trisaccharide binding are consistent with the observation of, a tighter complex with the trisaccharide than the pentasaccharide., Thermodynamic data demonstrate that the native tri- to pentasaccharides, have free energies of binding in the range of 6.8-7.4 kcal mol(-1), and, all but one of the hydrogen bonds to individual hydroxyl groups provide no, more than approximately 0.7 kcal mol(-1). They further indicate that, hydrophobic interactions make significant contributions to binding and, as, the native epitope becomes larger across the tri-, tetra-, pentasaccharide, series, entropy contributions to the free energy become dominant.
About this StructureAbout this Structure
1M71 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Molecular recognition of oligosaccharide epitopes by a monoclonal Fab specific for Shigella flexneri Y lipopolysaccharide: X-ray structures and thermodynamics., Vyas NK, Vyas MN, Chervenak MC, Johnson MA, Pinto BM, Bundle DR, Quiocho FA, Biochemistry. 2002 Nov 19;41(46):13575-86. PMID:12427018
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