NMR and Molecular Dynamics Studies of the Conformational Epitope of the Type III Group B Streptococcus Capsular Polysaccharide and Derivatives

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• 作者：Jean-Robert Brisson ; Stanislava Uhrinova ; Robert J. Woods ; Mark van der Zwan ; Harold C. Jarrell ; Lawrence C. Paoletti ; Dennis L. Kasper ; and Harold J. Jennings
• 刊名：Biochemistry
• 出版年：1997
• 出版时间：March 18, 1997
• 年：1997
• 卷：36
• 期：11
• 页码：3278 - 3292
• 全文大小：434K
• 年卷期：v.36,no.11(March 18, 1997)
• ISSN：1520-4995

文摘

The conformational epitope of the type III group BStreptococcus capsular polysaccharide(GBSP III) exhibits unique properties which can be ascribed to thepresence of sialic acid in its structureand the requirement for an extended binding site. By means of NMRand molecular dynamics studies onGBSP III and its fragments, the extended epitope of GBSP III wasfurther defined. The influence ofsialic acid on the conformational properties of GBSP III was examinedby performing conformationalanalysis on desialylated GBSP III, which is identical to thepolysaccharide of Streptococcuspneumoniaetype 14, and also on oxidized and reduced GBSP III. Conformationalchanges were gauged by ¹H and¹³C chemical shift analysis, NOE, 1D selectiveTOCSY-NOESY experiments, J_HH andJ_CH variations,and NOE of OH resonances. Changes in mobility were examined by¹³C T₁ and T₂measurements.Unrestrained molecular dynamics simulations with explicit waterusing the AMBER force field and theGLYCAM parameter set were used to assess static and dynamicconformational models, simulate theobservable NMR parameters and calculate helical parameters. GBSPIII was found to be capable offorming extended helices. Hence, the length dependence of theconformational epitope could be explainedby its location on extended helices within the random coil structure ofGBSP III. The interaction ofsialic acid with the backbone of the PS was also found to be importantin defining the conformationalepitope of GBSP III.