Homology modeling of human Fyn kinase structure: discovery of rosmarinic acid as a new Fyn kinase inhibitor and in silico study of its possible binding modes

J Med Chem. 2007 Mar 22;50(6):1090-100. doi: 10.1021/jm0607202. Epub 2007 Feb 22.


Tyrosine phosphorylation represents a unique signaling process that controls metabolic pathways, cell activation, growth and differentiation, membrane transport, apoptosis, neural, and other functions. We present here the three-dimensional structure of Fyn tyrosine kinase, a Src-family enzyme involved in T-cell receptor signal transduction. The structure of Fyn was modeled for homology using the Sybyl-Composer suite of programs for modeling. Procheck and Prosa II programs showed the high quality of the obtained three-dimensional model. Rosmarinic acid, a secondary metabolite of herbal plants, was discovered as a new Fyn kinase inhibitor using immunochemical and in silico methods. Two possible binding modes of rosmarinic acid were evaluated here, i.e., near to or in the ATP-binding site of kinase domain of Fyn. Enzyme kinetic experiments revealed that Fyn is inhibited by a linear-mixed noncompetitive mechanism of inhibition by rosmarinic acid. This indicates that rosmarinic acid binds to the second "non-ATP" binding site of the Fyn tyrosine kinase.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cinnamates / chemistry*
  • Depsides / chemistry*
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-fyn / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-fyn / chemistry*
  • Rosmarinic Acid
  • Sequence Homology, Amino Acid


  • Cinnamates
  • Depsides
  • Proto-Oncogene Proteins c-fyn