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The ß-reducing end in α(2-8)-polysialic acid constitutes a unique structural motif.
Azurmendi, Hugo F; Battistel, Marcos D; Zarb, Jasmin; Lichaa, Flora; Negrete Virgen, Alejandro; Shiloach, Joseph; Freedberg, Darón I.
Afiliación
  • Azurmendi HF; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
  • Battistel MD; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
  • Zarb J; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
  • Lichaa F; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
  • Negrete Virgen A; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
  • Shiloach J; Biotechnology Unit, MSC 5522, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Freedberg DI; Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
Glycobiology ; 27(9): 900-911, 2017 09 01.
Article en En | MEDLINE | ID: mdl-28369425
Over the years, structural characterizations of α(2-8)-polysialic acid (polySia) in solution have produced inconclusive results. Efforts for obtaining detailed information in this important antigen have focused primarily on the α-linked residues and not on the distinctive characteristics of the terminal ones. The thermodynamically preferred anomeric configuration for the reducing end of sialic acids is ß, which has the [I]CO2- group equatorial and the OH ([I]OH2) axial, while for all other residues the CO2- group is axial. We show that this purportedly minor difference has distinct consequences for the structure of α(2-8)-polySia near the reducing end, as the ß configuration places the [I]OH2 in a favorable position for the formation of a hydrogen bond with the carboxylate group of the following residue ([II]CO2-). Molecular dynamics (MD) simulations predicted the hydrogen bond, which we subsequently directly detected by NMR. The combination of MD and residual dipolar couplings shows that the net result for the structure of Sia2-ßOH is a stable conformation with well-defined hydration and charge patterns, and consistent with experimental NOE-based hydroxyl and aliphatic inter-proton distances. Moreover, we provide evidence that this distinct conformation is preserved on Sia oligosaccharides, thus constituting a motif that determines the structure and dynamics of α(2-8)-polySia for at least the first two residues of the polymer. We suggest the hypothesis that this structural motif sheds light on a longtime puzzling observation for the requirement of 10 residues of α(2-8)-polySia in order to bind effectively to specific antibodies, about four units more than for analogous cases.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ácidos Siálicos Tipo de estudio: Prognostic_studies Idioma: En Revista: Glycobiology Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ácidos Siálicos Tipo de estudio: Prognostic_studies Idioma: En Revista: Glycobiology Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos