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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

Ramachandran plot of the predicted model of HSD3B2 by (A) HHPred, (B) Phyre2 and (C) RaptorX server respectively. The plots were generated in PROCHECK. The most favored regions are colored red, additional allowed, generously allowed and disallowed regions are indicated as yellow, light yellow and white fields, respectively.
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f0025: Ramachandran plot of the predicted model of HSD3B2 by (A) HHPred, (B) Phyre2 and (C) RaptorX server respectively. The plots were generated in PROCHECK. The most favored regions are colored red, additional allowed, generously allowed and disallowed regions are indicated as yellow, light yellow and white fields, respectively.

Mentions: Validation of the model is very important in protein structural prediction since ultimately the modeled protein structure is used to design further experiments and understand the protein's biological function. A Ramachandran plot was obtained from PROCHECK for each of the generated pdb structures of HSD3B2. Fig. 5A, B and C showed the phi/psi Ramachandran plot of energy minimized HSD3B2 structures obtained from HHPred, Phyre2 and RaptorX server respectively. Total number of non-glycine and non-proline residues in the HSD3B2 structure is 329. Table 10 showed the analysis of Ramachandran Plot of modeled structures of HSD3B2. Protein backbone conformations were evaluated by inspection of the Ramachandran Plot which is an x–y plot of phi/psi dihedral angles between N-Cα and Cα-C planar peptide bonds in the protein's backbone. Both these angles are able to rotate freely in proteins (− 180 to + 180). Any combination of these angles is theoretically possible but in actual biological conditions many combinations are rarely or never seen due to steric clashes in the proteins' backbone structure.


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

Goswami AM - Meta Gene (2015)

Ramachandran plot of the predicted model of HSD3B2 by (A) HHPred, (B) Phyre2 and (C) RaptorX server respectively. The plots were generated in PROCHECK. The most favored regions are colored red, additional allowed, generously allowed and disallowed regions are indicated as yellow, light yellow and white fields, respectively.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0025: Ramachandran plot of the predicted model of HSD3B2 by (A) HHPred, (B) Phyre2 and (C) RaptorX server respectively. The plots were generated in PROCHECK. The most favored regions are colored red, additional allowed, generously allowed and disallowed regions are indicated as yellow, light yellow and white fields, respectively.
Mentions: Validation of the model is very important in protein structural prediction since ultimately the modeled protein structure is used to design further experiments and understand the protein's biological function. A Ramachandran plot was obtained from PROCHECK for each of the generated pdb structures of HSD3B2. Fig. 5A, B and C showed the phi/psi Ramachandran plot of energy minimized HSD3B2 structures obtained from HHPred, Phyre2 and RaptorX server respectively. Total number of non-glycine and non-proline residues in the HSD3B2 structure is 329. Table 10 showed the analysis of Ramachandran Plot of modeled structures of HSD3B2. Protein backbone conformations were evaluated by inspection of the Ramachandran Plot which is an x–y plot of phi/psi dihedral angles between N-Cα and Cα-C planar peptide bonds in the protein's backbone. Both these angles are able to rotate freely in proteins (− 180 to + 180). Any combination of these angles is theoretically possible but in actual biological conditions many combinations are rarely or never seen due to steric clashes in the proteins' backbone structure.

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