Figure 1
Correlation between experimental activities and predicted stabilities for Human and Bovine based templates.
A total of 30 mutants in human P450CYP21A2 protein with in vitro functional studies published up to 2013 were analyzed using either our own generated three-dimensional structure of CYP21 based on the bovine template PDB ID: 3QZ1 (A) or the human crystal structure PDB ID: 4Y8W (B). Only residues evaluated to impair protein function by means of protein stability were included. The predicted free energy change (∆∆G) upon mutation was plotted against the natural logarithm (ln) of the residual enzymatic activity on 17-OHP (A) or Progesterone (B) as substrates. A value of 5, 5 kcal/mol was considered as the maximum one for the fitting as higher destabilization will not impair activity below 0%. Spearman’s correlation coefficients were −0.894 and −0.829 for the 3QZ1 model and 4Y8W, respectively. These values were statistically significant (p < 0.001, permutation test). The values of the regression line slopes were also statistically significant (p < 0.001) ΔΔG is expressed in kcal/mol.
