% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Fierro:862977,
      author       = {Fierro, Fabrizio and Giorgetti, Alejandro and Carloni,
                      Paolo and Meyerhof, Wolfgang and Alfonso-Prieto, Mercedes},
      title        = {{D}ual binding mode of “bitter sugars” to their human
                      bitter taste receptor target},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2019-03130},
      pages        = {8437},
      year         = {2019},
      abstract     = {The 25 human bitter taste receptors (hTAS2Rs) are
                      responsible for detecting bitter molecules present in food,
                      and they also play several physiological and pathological
                      roles in extraoral compartments. Therefore, understanding
                      their ligand specificity is important both for food research
                      and for pharmacological applications. Here we provide a
                      molecular insight into the exquisite molecular recognition
                      of bitter β-glycopyranosides by one of the members of this
                      receptor subclass, hTAS2R16. Most of its agonists have in
                      common the presence of a β-glycopyranose unit along with an
                      extremely structurally diverse aglycon moiety. This poses
                      the question of how hTAS2R16 can recognize such a large
                      number of “bitter sugars”. By means of hybrid molecular
                      mechanics/coarse grained molecular dynamics simulations,
                      here we show that the three hTAS2R16 agonists salicin,
                      arbutin and phenyl-β-D-glucopyranoside interact with the
                      receptor through a previously unrecognized dual binding
                      mode. Such mechanism may offer a seamless way to fit
                      different aglycons inside the binding cavity, while
                      maintaining the sugar bound, similar to the strategy used by
                      several carbohydrate-binding lectins. Our prediction is
                      validated a posteriori by comparison with mutagenesis data
                      and also rationalizes a wealth of structure-activity
                      relationship data. Therefore, our findings not only provide
                      a deeper molecular characterization of the binding
                      determinants for the three ligands studied here, but also
                      give insights applicable to other hTAS2R16 agonists.
                      Together with our results for other hTAS2Rs, this study
                      paves the way to improve our overall understanding of the
                      structural determinants of ligand specificity in bitter
                      taste receptors.},
      cin          = {IAS-5 / INM-9},
      ddc          = {600},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
      pnm          = {574 - Theory, modelling and simulation (POF3-574)},
      pid          = {G:(DE-HGF)POF3-574},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31186454},
      UT           = {WOS:000470962100001},
      doi          = {10.1038/s41598-019-44805-z},
      url          = {https://juser.fz-juelich.de/record/862977},
}