4 research outputs found
Conformational Preferences of the OāAntigen Polysaccharides of Escherichia coli O5ac and O5ab Using NMR Spectroscopy and Molecular Modeling
Escherichia coli serogroup O5 comprises
two different subgroups (O5ab and O5ac), which are indiscernible from
the point of view of standard immunological serotyping. The structural
similarities between the O-antigen polysaccharides (PSs) of these
two strains are remarkable, with the only difference being the glycosidic
linkage connecting the biological tetrasaccharide repeating units.
In the present study, a combination of NMR spectroscopy and molecular
modeling methods were used to elucidate the conformational preferences
of these two PSs. The NMR study was based on the analysis of intra-
and inter-residue protonāproton distances using NOE build-up
curves. Molecular models of the repeating units and their extension
to polysaccharides were obtained, taking into account the conformational
flexibility as assessed by the force field applied and a genetic algorithm.
The agreements between experimentally measured and calculated distances
could only be obtained by considering an averaging of several low
energy conformations observed in the molecular models
Conformational Preferences of the OāAntigen Polysaccharides of Escherichia coli O5ac and O5ab Using NMR Spectroscopy and Molecular Modeling
Escherichia coli serogroup O5 comprises
two different subgroups (O5ab and O5ac), which are indiscernible from
the point of view of standard immunological serotyping. The structural
similarities between the O-antigen polysaccharides (PSs) of these
two strains are remarkable, with the only difference being the glycosidic
linkage connecting the biological tetrasaccharide repeating units.
In the present study, a combination of NMR spectroscopy and molecular
modeling methods were used to elucidate the conformational preferences
of these two PSs. The NMR study was based on the analysis of intra-
and inter-residue protonāproton distances using NOE build-up
curves. Molecular models of the repeating units and their extension
to polysaccharides were obtained, taking into account the conformational
flexibility as assessed by the force field applied and a genetic algorithm.
The agreements between experimentally measured and calculated distances
could only be obtained by considering an averaging of several low
energy conformations observed in the molecular models
Conformational Preferences of the OāAntigen Polysaccharides of Escherichia coli O5ac and O5ab Using NMR Spectroscopy and Molecular Modeling
Escherichia coli serogroup O5 comprises
two different subgroups (O5ab and O5ac), which are indiscernible from
the point of view of standard immunological serotyping. The structural
similarities between the O-antigen polysaccharides (PSs) of these
two strains are remarkable, with the only difference being the glycosidic
linkage connecting the biological tetrasaccharide repeating units.
In the present study, a combination of NMR spectroscopy and molecular
modeling methods were used to elucidate the conformational preferences
of these two PSs. The NMR study was based on the analysis of intra-
and inter-residue protonāproton distances using NOE build-up
curves. Molecular models of the repeating units and their extension
to polysaccharides were obtained, taking into account the conformational
flexibility as assessed by the force field applied and a genetic algorithm.
The agreements between experimentally measured and calculated distances
could only be obtained by considering an averaging of several low
energy conformations observed in the molecular models
The Hidden Conformation of Lewis x, a Human Histo-Blood Group Antigen, Is a Determinant for Recognition by Pathogen Lectins
Histo-blood group epitopes are fucosylated
branched oligosaccharides
with well-defined conformations in solution that are recognized by
receptors, such as lectins from pathogens. We report here the results
of a series of experimental and computational endeavors revealing
the unusual distortion of histo-blood group antigens by bacterial
and fungal lectins. The Lewis x trisaccharide adopts a rigid closed
conformation in solution, while crystallography and molecular dynamics
reveal several higher energy open conformations when bound to the <i>Ralstonia solanacearum</i> lectin, which is in agreement with
thermodynamic and kinetic measurements. Extensive molecular dynamics
simulations confirm rare transient Le<sup>x</sup> openings in solution,
frequently assisted by distortion of the central N-acetyl-glucosamine
ring. Additional directed molecular dynamic trajectories revealed
the role of a conserved tryptophan residue in guiding the fucose into
the binding site. Our findings show that conformational adaptation
of oligosaccharides is of paramount importance in cell recognition
and should be considered when designing anti-infective glyco-compounds