Structural modeling and in silico analysis of non-synonymous single nucleotide polymorphisms of human 3?-hydroxysteroid dehydrogenase type 2.

ABSTRACT: Single-nucleotide polymorphisms (SNPs), a most common type of genetic mutations, result from single base pair alterations. Non-synonymous SNPs (nsSNP) occur in the coding regions of a gene and result in single amino acid substitution which might have the potential to affect the function as well as structure of the corresponding protein. In human the 3?-hydroxysteroid dehydrogenases/?(4,5)-isomerase type 2 (HSD3B2) is an important membrane-bound enzyme involved in the dehydrogenation and ?(4,5)-isomerization of the ?(5)-steroid precursors into their respective ?(4)-ketosteroids in the biosynthesis of steroid hormones such as glucocorticoids, mineralocorticoids, progesterone, androgens, and estrogens in tissues such as adrenal gland, ovary, and testis. Most of the nsSNPs of HSD3B2 are still uncharacterized in terms of their disease causing potential. So, this study has been undertaken to explore and extend the knowledge related to the effect of nsSNPs on the stability and function of the HSD3B2. In this study sixteen nsSNP of HSD3B2 were subjected to in silico analysis using nine different algorithms: SIFT, PROVEAN, PolyPhen, MutPred, SNPeffect, nsSNP Analyzer, PhD SNP, stSNP, and I Mutant 2.0. The results obtained from the analysis revealed that the prioritization of diseases associated amino acid substitution as evident from possible alteration in structure-function relationship. Structural phylogenetic analysis using ConSurf revealed that the functional residues are highly conserved in human HSD3B2; and most of the disease associated nsSNPs are within these conserved residues. Structural theoritical models of HSD3B2 were created using HHPred, Phyre2 and RaptorX server. The predicted models were evaluated to get the best one for structural understanding of amino acid substitutions in three dimensional spaces.

SUBMITTER: Goswami AM 

PROVIDER: S-EPMC4539073 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature