Structure-based protein stability prediction and in vitro activity validation of human CYP21A2 mutants.

CARLOS DAVID BRUQUE, MARISOL DELEA, LILIANA DAIN AND ALEJANDRO DANIEL NADRA

Congreso; 4to. Congreso Argentino de Bioinformática y Biología Computacional (4CAB2C) y 4ta. Conferencia Internacional de la Sociedad Iberoamericana de Bioinformática (SolBio); 2013

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (OMIM 201910) accounts for 90?95% of CAH cases. This autosomal recessive disease, which is the most frequent inborn metabolic disorder, has a broad spectrum of clinical forms ranging from severe to mild. Severe or classical variants include salt-wasting and simple virilizing forms. On the other hand, non-classical variants are milder and of late onset forms of CAH1. In previous work, human 21-hydroxylase was shaped from different P450 cytochrome family crystallized proteins in order to predict the deleterious effects of novel mutations in the CYP21A2 gene2. Recently, however, the crystallography of the bovine 21-hydroxylase was obtained (OID:3QZ1) with a 80% sequence identity to the human one.Aim: Model human 21-hydroxylase using the bovine protein as template to further analyze protein stability of a set of already described mutations.