DOI: 10.1101/500645Dec 18, 2018Paper

Impact of branching on the conformational heterogeneity of the lipopolysaccharide from Klebsiella pneumoniae: Implications for vaccine design

BioRxiv : the Preprint Server for Biology
Asaminew H AytenfisuAlexander D MacKerell

Abstract

Resistance of Klebsiella pneumoniae (KP) to antibiotics has motivated the development of an efficacious KP human vaccine that would not be subject to antibiotic resistance. Klebsiella lipopolysaccharide (LPS) associated O polysaccharide (OPS) types have provoked broad interest as a vaccine antigen as there are only 4 that predominate worldwide (O1, O2a, O3, O5). Klebsiella O1 and O2 OPS are polygalactans that share a common D-Gal-I structure, for which a variant D-Gal-III was recently discovered. To understand the potential impact of this variability on antigenicity, a detailed molecular picture of the conformational differences associated with the addition of the D-Gal-III (1?4)Gal branch is presented using enhanced-sampling molecular dynamics simulations. In D-Gal-I two major conformational states are observed while the presence of the 1?4 branch in D-Gal-III resulted in only a single dominant extended state. Stabilization of the more folded states in D-Gal-I is due to a O4-H…O2 hydrogen bond in the linear backbone that cannot occur in D-Gal-III as the O4 is in the Galp(1?4)Galp glycosidic linkage. The impact of branching in D-Gal-III also significantly decreases the accessibility of the monosaccharides in the linear backbone...Continue Reading

Related Concepts

Klebsiella pneumoniae
Antibiotics
Epitopes
Antigens
Classification
Klebsiella
Lipopolysaccharides
Monosaccharides
Oxygen
Ozone

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