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

Goswami AM - Meta Gene (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Krishnagar Govt. College, Krishnagar, Nadia, West Bengal, India.

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 3β-hydroxysteroid dehydrogenases/Δ(4,5)-isomerase type 2 (HSD3B2) is an important membrane-bound enzyme involved in the dehydrogenation and Δ(4,5)-isomerization of the Δ(5)-steroid precursors into their respective Δ(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.

No MeSH data available.


Related in: MedlinePlus

Homology based prediction of HSD3B2 structure using HHPred (A), Phyre (B) and RaptorX (C) web-based server. The visual images of the structures were generated in PyMol.
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f0015: Homology based prediction of HSD3B2 structure using HHPred (A), Phyre (B) and RaptorX (C) web-based server. The visual images of the structures were generated in PyMol.

Mentions: The ability of the protein to interact with other molecules or to have different functions depends upon its tertiary structure (Hasan et al., 2011; Alshatwi et al., 2011). Therefore, analysis of damaged coding nsSNPs at the structural level is necessary to understand the activity of the protein. There is no crystal structure of HSD3B2 available in the protein data bank. So the 3D structure of HSD3B2 has been modeled using the available protein sequence for homology based modeling. Web based servers like HHPred, Phyre 2 and Raptor X are used for homology modeling of HSD3B2. Fig. 3A, B and C were cartoon representation of the protein structure obtained from HHPred server, Phyre2 server and RaptorX server respectively. HHpred profiles are calculated from a multiple sequence alignment of related sequences which are typically collected using the PSI-BLAST program. Phyre2 uses the Hidden Markov Method to generate alignments of a submitted protein sequence against proteins with published structures. RaptorX uses a non-linear scoring function to combine homologous information with structural information for a given template-sequence alignment.


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

Goswami AM - Meta Gene (2015)

Homology based prediction of HSD3B2 structure using HHPred (A), Phyre (B) and RaptorX (C) web-based server. The visual images of the structures were generated in PyMol.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539073&req=5

f0015: Homology based prediction of HSD3B2 structure using HHPred (A), Phyre (B) and RaptorX (C) web-based server. The visual images of the structures were generated in PyMol.
Mentions: The ability of the protein to interact with other molecules or to have different functions depends upon its tertiary structure (Hasan et al., 2011; Alshatwi et al., 2011). Therefore, analysis of damaged coding nsSNPs at the structural level is necessary to understand the activity of the protein. There is no crystal structure of HSD3B2 available in the protein data bank. So the 3D structure of HSD3B2 has been modeled using the available protein sequence for homology based modeling. Web based servers like HHPred, Phyre 2 and Raptor X are used for homology modeling of HSD3B2. Fig. 3A, B and C were cartoon representation of the protein structure obtained from HHPred server, Phyre2 server and RaptorX server respectively. HHpred profiles are calculated from a multiple sequence alignment of related sequences which are typically collected using the PSI-BLAST program. Phyre2 uses the Hidden Markov Method to generate alignments of a submitted protein sequence against proteins with published structures. RaptorX uses a non-linear scoring function to combine homologous information with structural information for a given template-sequence alignment.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Krishnagar Govt. College, Krishnagar, Nadia, West Bengal, India.

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 3β-hydroxysteroid dehydrogenases/Δ(4,5)-isomerase type 2 (HSD3B2) is an important membrane-bound enzyme involved in the dehydrogenation and Δ(4,5)-isomerization of the Δ(5)-steroid precursors into their respective Δ(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.

No MeSH data available.


Related in: MedlinePlus