Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Alshatwi, Ali A.; Hasan, Tarique N.; Syed, Naveed Ahmed; Shafi, Gowhar

doi:10.6026/97320630007334

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…The ability of the protein to interact with other molecules or to have different functions depends upon its tertiary structure [47] , [48] . Therefore, analysis of damaged coding nsSNPs at the structural level is necessary to understand the activity of the protein.…”

Section: Methodsmentioning

confidence: 99%

Identification of Functional SNPs in BARD1 Gene and In Silico Analysis of Damaging SNPs: Based on Data Procured from dbSNP Database

et al. 2012

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BackgroundThe BARD1 gene encodes for the BRCA1-associated RING domain (BARD1) protein. Germ line and somatic mutations in BARD1 are found in sporadic breast, ovarian and uterine cancers. There is a plethora of single nucleotide polymorphisms (SNPs) which may or may not be involved in the onset of female cancers. Hence, before planning a larger population study, it is advisable to sort out the possible functional SNPs. To accomplish this goal, data available in the dbSNP database and different computer programs can be used. To the best of our knowledge, until now there has been no such study on record for the BARD1 gene. Therefore, this study was undertaken to find the functional nsSNPs in BARD1.Result2.85% of all SNPs in the dbSNP database were present in the coding regions. SIFT predicted 11 out of 50 nsSNPs as not tolerable and PolyPhen assessed 27 out of 50 nsSNPs as damaging. FastSNP revealed that the rs58253676 SNP in the 3′ UTR may have splicing regulator and enhancer functions. In the 5′ UTR, rs17489363 and rs17426219 may alter the transcriptional binding site. The intronic region SNP rs67822872 may have a medium-high risk level. The protein structures 1JM7, 3C5R and 2NTE were predicted by PDBSum and shared 100% similarity with the BARD1 amino acid sequence. Among the predicted nsSNPs, rs4986841, rs111367604, rs13389423 and rs139785364 were identified as deleterious and damaging by the SIFT and PolyPhen programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Finally, the ExPASy-PROSIT program revealed that the predicted deleterious mutations are contained in the ankyrin ring and BRCT domains.ConclusionUsing the available bioinformatics tools and the data present in the dbSNP database, the four nsSNPs, rs4986841, rs111367604, rs13389423 and rs139785364, were identified as deleterious, reducing the protein stability of BARD1. Hence, these SNPs can be used for the larger population-based studies of female cancers.

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Section: Methodsmentioning

confidence: 99%

Identification of Functional SNPs in BARD1 Gene and In Silico Analysis of Damaging SNPs: Based on Data Procured from dbSNP Database

et al. 2012

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“…Deleterious high risk nsSNPs predicted by analysis were subjected to 3D-structure analysis. The ability of proteins to perform various functions or to interact with other molecules depends upon its tertiary structure (Alshatwi et al, 2011 ). To predict the 3D-structure of pentraxin-domain homology modeling was performed by using Phyre-2 server.…”

Section: Resultsmentioning

confidence: 99%

In silico Analysis Revealed High-risk Single Nucleotide Polymorphisms in Human Pentraxin-3 Gene and their Impact on Innate Immune Response against Microbial Pathogens

Thakur

Shankar

2016

Front. Microbiol.

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Pentraxin-3 (PTX-3) protein is an evolutionary conserved protein that acts as a soluble pattern-recognition receptor for pathogens and plays important role in innate immune response. It recognizes various pathogens by interacting with extracellular moieties such as glactomannan of conidia (Aspergillus fumigatus), lipopolysaccharide of Pseudomonas aeruginosa, Streptococcus pneumonia and Salmonella typhimurium. Thus, PTX-3 protein helps to clear these pathogens by activating downstream innate immune process. In this study, computational methods were used to analyze various non-synonymous single nucleotide polymorphisms (nsSNPs) in PTX-3 gene. Three different databases were used to retrieve SNP data sets followed by seven different in silico algorithms to screen nsSNPs in PTX-3 gene. Sequence homology based approach was used to identify nsSNPs. Conservation profile of PTX-3 protein amino acid residues were predicted by ConSurf web server. In total, 10 high-risk nsSNPs were identified in pentraxin-domain of PTX-3 gene. Out of these 10 high-risk nsSNPs, 4 were present in the conserved structural and functional residues of the pentraxin-domain, hence, selected for structural analyses. The results showed alteration in the putative structure of pentraxin-domain. Prediction of protein–protein interactions analysis showed association of PTX-3 protein with C1q component of complement pathway. Different functional and structural residues along with various putative phosphorylation sites and evolutionary relationship were also predicted for PTX-3 protein. This is the first extensive computational analyses of pentraxin protein family with nsSNPs and will serve as a valuable resource for future population based studies.

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“…The ability of the protein to interact with other molecules or to have different functions depends upon its tertiary structure ( Hasan, TN, et al, 2011 , Alshatwi, AA, et al, 2011 ). Therefore, analysis of damaged coding nsSNPs at the structural level is necessary to understand the activity of the protein.…”

Section: Resultsmentioning

confidence: 99%

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

Goswami¹

2015

Meta Gene

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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/Δ4,5-isomerase type 2 (HSD3B2) is an important membrane-bound enzyme involved in the dehydrogenation and Δ4,5-isomerization of the Δ5-steroid precursors into their respective Δ4-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.

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Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Cited by 6 publications

References 20 publications

Identification of Functional SNPs in BARD1 Gene and In Silico Analysis of Damaging SNPs: Based on Data Procured from dbSNP Database

Identification of Functional SNPs in BARD1 Gene and In Silico Analysis of Damaging SNPs: Based on Data Procured from dbSNP Database

In silico Analysis Revealed High-risk Single Nucleotide Polymorphisms in Human Pentraxin-3 Gene and their Impact on Innate Immune Response against Microbial Pathogens

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

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