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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

Analysis of evolutionary conserved amino acid residues of HSD3B2 by ConSurf. The color coding bar shows the coloring scheme representation of conservation score.
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f0005: Analysis of evolutionary conserved amino acid residues of HSD3B2 by ConSurf. The color coding bar shows the coloring scheme representation of conservation score.

Mentions: The results generated by the ConSurf tool consist of a structural representation of the protein (Fig. 1) which contain a colorimetric conservation score. Evolutionary information is of fundamental importance for detecting mutations that affect human health (Ramensky et al., 2002). ConSurf identifies functional regions in proteins, taking into account the evolutionary relationships among their sequence homologs (Glaser et al., 2003). The ConSurf conservation analysis was performed by evolutionarily related conservation scores of the residues for functional region identification from proteins of known three dimensional structures (Jimenez-Lopez et al., 2010). The ConSurf analysis also revealed, as expected, that the functional regions of the protein are highly conserved. It was observed that variants A10E, E142K, T259M, and P341L have a conservation scale of 9; G2V and D74N have a conservation scale of 8; P222T has a conservation scale of 7; L236S and R316C have a conservation scale of 6 and V19A has a conservation scale of 5.


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

Goswami AM - Meta Gene (2015)

Analysis of evolutionary conserved amino acid residues of HSD3B2 by ConSurf. The color coding bar shows the coloring scheme representation of conservation score.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0005: Analysis of evolutionary conserved amino acid residues of HSD3B2 by ConSurf. The color coding bar shows the coloring scheme representation of conservation score.
Mentions: The results generated by the ConSurf tool consist of a structural representation of the protein (Fig. 1) which contain a colorimetric conservation score. Evolutionary information is of fundamental importance for detecting mutations that affect human health (Ramensky et al., 2002). ConSurf identifies functional regions in proteins, taking into account the evolutionary relationships among their sequence homologs (Glaser et al., 2003). The ConSurf conservation analysis was performed by evolutionarily related conservation scores of the residues for functional region identification from proteins of known three dimensional structures (Jimenez-Lopez et al., 2010). The ConSurf analysis also revealed, as expected, that the functional regions of the protein are highly conserved. It was observed that variants A10E, E142K, T259M, and P341L have a conservation scale of 9; G2V and D74N have a conservation scale of 8; P222T has a conservation scale of 7; L236S and R316C have a conservation scale of 6 and V19A has a conservation scale of 5.

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