NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives

Biochemistry. 1997 Mar 18;36(11):3278-92. doi: 10.1021/bi961819l.

Abstract

The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Epitopes / chemistry*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Models, Theoretical
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Peptide Fragments / chemistry
  • Polysaccharides, Bacterial / chemistry*
  • Polysaccharides, Bacterial / immunology
  • Streptococcus agalactiae / immunology*

Substances

  • Epitopes
  • Oligosaccharides
  • Peptide Fragments
  • Polysaccharides, Bacterial