Structure-based activity prediction of CYP21A2 stability variants: A survey of available gene variations.

ABSTRACT: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90-95% of CAH cases. In this work we performed an extensive survey of mutations and SNPs modifying the coding sequence of the CYP21A2 gene. Using bioinformatic tools and two plausible CYP21A2 structures as templates, we initially classified all known mutants (n = 343) according to their putative functional impacts, which were either reported in the literature or inferred from structural models. We then performed a detailed analysis on the subset of mutations believed to exclusively impact protein stability. For those mutants, the predicted stability was calculated and correlated with the variant's expected activity. A high concordance was obtained when comparing our predictions with available in vitro residual act

SUBMITTER: Bruque CD 

PROVIDER: S-EPMC5155424 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature