% 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{Maier:299820,
      author       = {P. Maier and M. Macht and S. Beck and P. Kolkhir and M.
                      Babina and A. E. Kremer and D. Zahn and K. Wolf$^*$},
      title        = {{MRGPRX}2 ligandome: {M}olecular simulations reveal three
                      categories of ligand-receptor interactions.},
      journal      = {Journal of structural biology},
      volume       = {217},
      number       = {2},
      issn         = {1047-8477},
      address      = {San Diego, Calif.},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00557},
      pages        = {108193},
      year         = {2025},
      note         = {#LA:D190# / Volume 217, Issue 2, June 2025, 108193 /
                      HI-TRON Mainz},
      abstract     = {Mas-related G protein-coupled receptor (MRGPR) X2 is a mast
                      cell receptor known to be activated by a wide range of
                      ligands of various size, charge and origin. Our aim is to
                      gain a deeper understanding of the binding processes of the
                      different MRGPRX2 ligands and the ligand-receptor
                      interactions in order to identify crucial structural
                      elements for receptor activation.We used the
                      three-dimensional structure of MRGPRX2 described in Nature
                      in 2021 by Cao et al. and Yang et al. to computationally
                      model the interaction between MRGPRX2 and small molecule
                      ligands under simulated physiological conditions.Docking and
                      post-docking samplings of the MRGPRX2 ligandome within the
                      GPCR binding pocket led to the identification of key
                      structural features for protein-ligand interactions. On the
                      ligand side, we obtained an overlay of different molecular
                      patterns or chemical groups by comparing different ligands
                      plotted on the receptor. These key features include at least
                      one protonated amine moiety of MRGPRX2 ligands contributing
                      to one salt-bridge and one π-cation interaction, as well as
                      an extended non-polar domain of the ligand surface that
                      offer hydrophobic segregation and/or π-stacking
                      interactions. In the receptor, we identified amino acids
                      (GLU164, ASP184, PHE101, PHE170, TRP243, PHE244 and PHE257)
                      that specifically interact via hydrogen bonding,
                      salt-bridges, π-cation interactions and π-π stacking with
                      the ligands to direct binding and ultimately receptor
                      activation.Our insights into ligand-receptor interaction
                      obtained by molecular modeling can help to predict mast cell
                      activation via MRGPRX2 including adverse reactions, and
                      facilitate the development of MRGPRX2 antagonists for the
                      treatment of mast cell-mediated diseases.},
      keywords     = {Docking (Other) / Ligand-receptor interaction (Other) /
                      Mas-related G protein coupled receptor X2 (Other) /
                      Molecular recognition (Other) / Pharmacophore (Other)},
      cin          = {D190},
      ddc          = {540},
      cid          = {I:(DE-He78)D190-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40086706},
      doi          = {10.1016/j.jsb.2025.108193},
      url          = {https://inrepo02.dkfz.de/record/299820},
}