Unraveling the
Structural Consequence of Pathogenic Single Nucleotide Polymorphisms in the Human
Aldosterone Synthase: An in silico Approach
Dhamodharan Prabhu, Murugan Mukilan, Muthu Krishnan Dhivya Dharshini, Vairavanathan
Jayavarshini and Gopalakrishnan Velliyur Kanniappan
Res. J. Biotech.; Vol. 20(11); 30-41;
doi: https://doi.org/10.25303/2011rjbt030041; (2025)
Abstract
Aldosterone is an essential hormone secreted by adrenal glands playing a major role
in the regulation of blood pressure. The secretion of aldosterone depends on the
regulation of aldosterone synthase through the CYP11B2 (cytochrome P450 family 11
subfamily B member 2) gene in the zona glomerulosa layer of adrenal glands. The
CYP11B2 gene plays a major role in the development of essential hypertension through
the conversion of deoxycorticosterone to aldosterone. Recent studies have shown
that polymorphism in CYP11B2 has a relationship with the development of hypertension.
It also showed that the CYP11B2 gene single nucleotide polymorphism (SNP) may play
a major role in the development of disorders like diabetes, hypertension, myocardial
infarction etc. The present study made an initial attempt to study the effect of
selective SNP mutation in the CYP11B2 protein structure modifications and its impact
on aldosterone synthase production. This present study uses a bioinformatics database
(uniprot) for protein sequence retrieval of CYP11B2.
The retrieved protein sequence of CYP11B2 was used for the creation of mutant structures
(pathogenic, benign and like benign) with the help of a molecular modeling approach
(Schrödinger Molecular Modeling Suite). The effect of created single-point mutations
on protein stability was studied with the help of a computational tool (Dynamut).
The outcome of the present study showed that selective pathogenic mutations severely
impact the function of CYP11B2 proteins compared to benign and likely begin structures.
It also proved that pathogenic mutations may also lead to structural changes in
the CYP11B2 protein. The outcome of the present study showed that SNP may have a
varying impact on the CYP11B2 protein functions through structural differentiations.
