Figure 2.

Analysis of the structure and molecular dynamics of the DYRK1A-E396ter protein. (a) Crystal structure of the human DYRK1A kinase domain in complex with its inhibitor, DJM2005 (PDB ID: 4MQ2) and substrate peptide is shown on the left. The C-helix, activation segment, catalytic loop, and CMGC insert are coloured in red, blue, orange, and hot pink, respectively. The N- and C-termini of the kinase domain of DYRK1A are represented by blue and red circles, respectively. The substrate peptide and inhibitor, DJM2005, are represented by a ball and stick model and coloured in dark and light grey, respectively. The predicted structure of DYRK1A-E396ter in complex with DJM2005 is shown on the right. The peptide sequences, which were not expressed in the mutant, are coloured dark grey and the location of the mutation (E396ter) is indicated by a red arrow. (b) Energy minimization of the wild-type and E396ter DYRK1A proteins was performed by using the MODELLER software, and the local molecular dynamics were assessed by using the Dynamut webserver with normal mode analysis function. Resulting molecular dynamics of the wild-type and E396ter DYRK1A proteins are presented in a tube style, which was generated by using PyMol software (version 1.3). The deformation energy is represented by thin to thick tubes coloured in blue (low), white (moderate), and red (high). (c) The deformation energy of the wild-type and E396ter DYRK1A proteins are coloured in blue and red, respectively.