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

Carbohydrate Research
Asaminew AytenfisuAlexander 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)-α-Galp 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 linea...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Sep 25, 1997·Clinical and Diagnostic Laboratory Immunology·M TrautmannC Whitfield
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Jan 22, 2004·Journal of the American Chemical Society·Alexander D MacKerellCharles L Brooks
Apr 22, 2004·Journal of Molecular Graphics & Modelling·Michael FeigCharles L Brooks
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Pu LiuB J Berne
Apr 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·S J Wodak, J Janin
May 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Renuka KadirvelrajRobert J Woods
May 13, 2008·Journal of Computational Chemistry·Olgun GuvenchAlexander D Mackerell
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Sep 18, 2010·The Journal of Physical Chemistry. B·E Prabhu RamanAlexander D MacKerell
Jan 15, 2013·Journal of Chemical Theory and Computation·Peter EastmanVijay S Pande
Apr 27, 2012·Infectious Disease Reports·Tarek A AhmadLaila H El-Sayed
Aug 29, 2014·F1000prime Reports·Christopher A BrobergVirginia L Miller
Feb 7, 2015·Carbohydrate Research·Michelle M KuttelNeil Ravenscroft
Jun 18, 2015·Journal of Chemical Theory and Computation·Mingjun YangAlexander D MacKerell
Sep 8, 2015·Pathogens and Global Health·Francesca PrestinaciAnnalisa Pantosti
Jan 3, 2016·International Journal of Medical Microbiology : IJMM·Valéria SzijártóGábor Nagy
Apr 21, 2017·The Journal of Physical Chemistry. B·Mingjun YangAlexander D MacKerell
May 11, 2017·Frontiers in Microbiology·Katarina StojkovicJolanta Lukasiewicz
Jul 2, 2017·Scientific Reports·Mingjun YangAlexander D MacKerell

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Citations

Sep 25, 2021·Journal of Chemical Information and Modeling·Cristina González-FernándezInmaculada Ortiz

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