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A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin.

ABSTRACT: The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Man?1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Man?1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by E. coli. Man?1,2Man has been described early on as shielding the (Man?1,3Man) glycan that is more relevant to strong bacterial adhesion and invasion. We quantified the binding of the two dimannoses (Man?1,2Man and Man?1,3Man to FimH using ELLSA and isothermal microcalorimetry and calculated probabilities of binding modes using molecular dynamics simulations. Our experimentally and computationally determined binding energies confirm a higher affinity of FimH towards the dimannose Man?1,3Man. Man?1,2Man displays a much lower binding enthalpy combined with a high entropic gain. Most remarkably, our molecular dynamics simulations indicate that Man?1,2Man cannot easily take its major conformer from water into the FimH binding site and that FimH is interacting with two very different conformers of Man?1,2Man that occupy 42% and 28% respectively of conformational space. The finding that Man?1,2Man binding to FimH is unstable agrees with the earlier suggestion that E. coli may use the Man?1,2Man epitope for transient tethering along cell surfaces in order to enhance dispersion of the infection.


PROVIDER: S-EPMC6278545 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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