Maria Beihaghi; Shima Ghasemi; Mohammad Reza Beihaghi; Nazanin Ataee; Mahsa Zabetian; Hanieh Hadizadeh
Abstract
Cytochromes are enzymes of the dehydrogenase class with a hemoprotein structure in which the iron in these compounds undergoes oxidation and reduction reactions upon receiving or losing electrons. Quantitatively speaking, CYP3A4 is the most important isoenzyme of cytochrome P450, oxidizing foreign organic ...
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Cytochromes are enzymes of the dehydrogenase class with a hemoprotein structure in which the iron in these compounds undergoes oxidation and reduction reactions upon receiving or losing electrons. Quantitatively speaking, CYP3A4 is the most important isoenzyme of cytochrome P450, oxidizing foreign organic molecules such as drugs or toxins to cause them to leave the body. Many drugs and antibiotics can induce or inhibit the activity of cytochrome P450, including dexamethasone. Dexamethasone is a steroidal anti-inflammatory drug used to treat of inflammatory diseases and chronic autoimmunity. This study aimed to investigate the induction effect of dexamethasone in biotransformation pathways by in silico tools. Molegro Virtual Docker software was used to investigate the molecular docking of the enzyme and dexamethasone, which indicated the binding of the drug to the enzyme. The molecular simulation was performed in Linux with the GROMACS program. Root-mean-square distance (RMSD), and radius of gyration (Rg), were evaluated. The results were analyzed with Pymol and VMD software, and the obtained curve was plotted with GRACE software. Docking results show that a cluster with a bond energy of -60.81 was the best cluster, and the bond size between ligand and internal atoms was -23.191in the complex. In addition, the amount of bond between the ligand and water for this pose was zero. The stability of the enzyme-ligand complex and the induction effect of dexamethasone on CYP3A4 were indicated by RMSD and RG results. Results of RMSD and RG of CYP3A4 glucocorticoid obtained from the simulation showed the stability of binding of the drug to the enzyme. Also, RMSD results showed the stability of glucocorticoid and dexamethasone complex during molecular dynamics simulation. It reached relative stability at 0.8 nm after 80,000 ps until the end of the simulation.
Ahdiyeh Shahtaghi; Ali Alam Shahnabadi; Kamelia Kohannezhad; Neda Amini; Maria Beihaghi
Abstract
One of the newest diagnostic methods and treatment of cancer is to design new drugs. It is now possible to design a drug with desired properties in theory and evaluate its therapeutic effects through bioinformatics tools. Among the studied drugs, those based on cytokine genes, which increase the body's ...
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One of the newest diagnostic methods and treatment of cancer is to design new drugs. It is now possible to design a drug with desired properties in theory and evaluate its therapeutic effects through bioinformatics tools. Among the studied drugs, those based on cytokine genes, which increase the body's immunity against cancer, are of great interest. Cytokines are small proteins that play an essential role in cell signaling and can affect the function and behavior of surrounding cells. CCL21 chemokine is one of the cytokines that possess antitumor properties has the potential for chemoattraction of T lymphocytes and dendritic cells. Interleukin 1 beta (IL1β) is a cytokine involving different cellular activities such as the activation of neutrophils, B-Cells, and T-Cells. In the present study, we designed a drug-based cytokine gene to activate T cells and B cells by inserting defined CCL21 epitope and IL1β peptide sequences into a protein construct. Molecular dynamics simulation was performed in Linux space using Gromex software. Results of RMSD, RMSF, and the radius of gyration obtained from the simulation showed the stability of both proteins, which indicated that there are no significant conformational differences between the commercial CCL21 and recombinant form. The interaction of synthetic construct and human CCL21 with the CCR7 receptor was also investigated by HADDOCK software. Obtained results showed no differences between these proteins, and recombinant protein has the same structural and conformational characteristics as human commercial CCL21.
Maria Beihaghi; Ahmad Reza Bahrami; Abdolreza Bagheri; Mohammad Zare Mehrjerdi
Abstract
Studies on the genes contributing to the seed filling in chickpea and its protein content might be valuable in engineering plants with seeds of a higher nutritional value. A gene of interest is phosphoenolpyruvate carboxykinase (pepck), encoding a protein with a substantial role in the gluconeogenesis ...
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Studies on the genes contributing to the seed filling in chickpea and its protein content might be valuable in engineering plants with seeds of a higher nutritional value. A gene of interest is phosphoenolpyruvate carboxykinase (pepck), encoding a protein with a substantial role in the gluconeogenesis pathway. In the present study, the protein content (percentage) was measured in a number of cultivated chickpea genotypes, followed by comparison of the expression levels of pepck gene at different stages of seed filling in some of the genotypes. This study aims at revealing the relation between pepck transcript level with protein content of chickpea seeds which might, in the longer term, end at protein quality improvement of the crop through the gene manipulation procedures. The results which were verified by Real Time-PCR and Western blot techniques in four genotypes of plant, showed that, the amount of pepck expression was significantly higher at the stage of seed fillingthan at other stages in all of genotypes and the lowest levels of expression belonged to flowering and seed formation and the PEPCK protein level was higher in the high protein genotypes compared to the low protein genotypes.
Ahmad Reza Bahrami; Maria Beihaghi; Abdolreza Bagheri; Richard Leegood; Mehdi Ghabooli; Jafar Zolala; Farajollah Shahriari
Abstract
Abstract
Phosphoenolpyruvate Carboxykinase, encoded by the pepck gene, plays an important role in
gluconeogenesis. It also seems to be important in metabolism of nitrogenous compounds in developing seeds of
legumes, including amides and ureides which are then transformed into amino acids, necessary ...
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Abstract
Phosphoenolpyruvate Carboxykinase, encoded by the pepck gene, plays an important role in
gluconeogenesis. It also seems to be important in metabolism of nitrogenous compounds in developing seeds of
legumes, including amides and ureides which are then transformed into amino acids, necessary for the
synthesis of storage proteins. In this research, pepck gene expression in mRNA level, in different genotypes of
chickpea (Cicer arietinum L.), was determined. Two low protein genotypes (MCC291 and MCC373) and two
high protein genotypes (MCC458 and MCC053) out of 20 chickpea genotypes were selected. Total RNA were
extracted through different stages of seed development, and the expression of the pepck gene was estimated by
semi-quantitative RT-PCR. The results of the RT-PCR showed that two isoforms of this gene are expressed in
high protein genotypes, whereas in the low protein genotypes, the expression of these isoforms was not
obvious. Also this method showed a differential expression of pepck gene in different stages of flowering and
seed development. pepck gene is expressed in higher levels during the sheet formation and developing seeds
compared to the flowering and seed formation stages. Probably, the differential expression of pepck gene is
related to its possible role in metabolism of seed components, particularly in determination of the protein
content of chickpea seeds.
