Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study.
| dc.contributor.author | Kuttel, Michelle Mary | |
| dc.contributor.author | Ravenscroft, Neil | |
| dc.date.accessioned | 2019-06-04T07:38:11Z | |
| dc.date.available | 2019-06-04T07:38:11Z | |
| dc.date.issued | 2019-02-13 | |
| dc.description.abstract | Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal β dGlc(1→6) β dGlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a “zig-zag” conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages. | en_US |
| dc.identifier.apacitation | Kuttel, M. M., & Ravenscroft, N. (2019). Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study. <i>Pharmaceuticals</i>, 12(1), 28. http://hdl.handle.net/11427/30191 | en_ZA |
| dc.identifier.chicagocitation | Kuttel, Michelle Mary, and Neil Ravenscroft "Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study." <i>Pharmaceuticals</i> 12, 1. (2019): 28. http://hdl.handle.net/11427/30191 | en_ZA |
| dc.identifier.citation | Kuttel, M. M., & Ravenscroft, N. (2019). Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study. Pharmaceuticals, 12(1), 28. | |
| dc.identifier.ris | TY - Journal Article AU - Kuttel, Michelle Mary AU - Ravenscroft, Neil AB - Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal β dGlc(1→6) β dGlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a “zig-zag” conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages. DA - 2019-02-13 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Pharmaceuticals KW - capsular polysaccharide LK - https://open.uct.ac.za PY - 2019 T1 - Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study TI - Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study UR - http://hdl.handle.net/11427/30191 ER - | en_ZA |
| dc.identifier.uri | 10.3390/ph12010028 | |
| dc.identifier.uri | https://www.mdpi.com/1424-8247/12/1/28 | |
| dc.identifier.uri | http://hdl.handle.net/11427/30191 | |
| dc.identifier.vancouvercitation | Kuttel MM, Ravenscroft N. Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study. Pharmaceuticals. 2019;12(1):28. http://hdl.handle.net/11427/30191. | en_ZA |
| dc.language.iso | en | en_US |
| dc.publisher.department | Department of Computer Science | en_US |
| dc.publisher.faculty | Faculty of Science | en_US |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
| dc.source | Pharmaceuticals | en_US |
| dc.source.journalissue | 1 | en_US |
| dc.source.journalvolume | 12 | en_US |
| dc.source.pagination | 28 | en_US |
| dc.source.uri | https://www.mdpi.com/journal/pharmaceuticals | |
| dc.subject | capsular polysaccharide | en_US |
| dc.subject.other | carbohydrate antigen | |
| dc.subject.other | molecular modeling | |
| dc.subject.other | Group B Streptococcus | |
| dc.subject.other | Streptococcus pneumoniae | |
| dc.subject.other | conjugate vaccines | |
| dc.title | Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study. | en_US |
| dc.type | Journal Article | en_US |