In all the mutants, the mutation sites are located within the Kelch-domain only. However, Further, we observed quite large fluctuations in the BTB-domain, especially at the Nterminal region for all the cases. The average value of the RMSD fluctuations for heavy atoms in the BTB-domain for all the cases ranges from 2.11Å to 3.24Å. The average RMSD value for the WT is 2.26Å (Fig. ) however, it is 2.11Å for the R539T which is the lowest value among all the mutants (Fig. ).