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Wyświetlanie 1-15 z 21
Tytuł:
Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach
Autorzy:
Ismail, Tariq
Fatima, Nighat
Muhammad, Syed
Zaidi, Syed
Rehman, Nisar
Hussain, Izhar
Tariq, Najam us
Amirzada, Imran
Mannan, Abdul
Powiązania:
https://bibliotekanauki.pl/articles/1038391.pdf
Data publikacji:
2018
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Candida albicans
drug target identification
protein modeling
Opis:
Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.
Źródło:
Acta Biochimica Polonica; 2018, 65, 2; 209-218
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Endothelium as target for large-conductance calcium-activated potassium channel openers
Autorzy:
Wrzosek, Antoni
Powiązania:
https://bibliotekanauki.pl/articles/1040527.pdf
Data publikacji:
2009
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
endothelium-derived hyperpolarising factor
potassium channels
endothelium
Opis:
The endothelium is a highly active organ responsible for vasculatory tone and structure, angiogenesis, as well as hemodynamic, humoral, and inflammatory responses. The endothelium is constantly exposed to blood flow, sheer stress and tension. Endothelial cells are present as a vasculature in every tissue of the body and react to and control its microenvironment. A variety of ion channels are present in the plasma membranes of endothelial cells. These include potassium channels such as inwardly rectifying potassium (Kir) channels, voltage-dependent (Kv) channels, ATP-regulated potassium (KATP) channels and three types of calcium-activated potassium channels (KCa), the large (BKCa), intermediate (IKCa), and small (SKCa) -conductance potassium channels. Potassium current plays a critical role in action potentials in excitable cells, in setting the resting membrane potential, and in regulating neurotransmitter release. Mitochondrial isoforms of potassium channel contribute to the cytoprotection of endothelial cells. Prominent among potassium channels are families of calcium-activated potassium channels, and especially large-conductance calcium-activated potassium channels. The modulation of BKCa channels, which are voltage- and calcium-dependent, has been intensively studied. The BKCa channels show large expression dynamics in endothelial cells and tissue-specific expression of large numbers of alternatively spliced isoforms. In this review, a few examples of the modulatory mechanisms and physiological consequences of the expression of BKCa channels are discussed in relation to potential targets for pharmacological intervention.
Źródło:
Acta Biochimica Polonica; 2009, 56, 3; 393-404
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
EF-1α Is a target site for an inhibitory effect of quercetin in the peptide elongation process
Autorzy:
Marcinkiewicz, Cezary
Gałasiński, Władysław
Gindzieński, Andrzej
Powiązania:
https://bibliotekanauki.pl/articles/1045226.pdf
Data publikacji:
1995
Wydawca:
Polskie Towarzystwo Biochemiczne
Źródło:
Acta Biochimica Polonica; 1995, 42, 3; 347-350
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Filarial glutathione S-transferase: its induction by xenobiotics and potential as drug target
Autorzy:
Gupta, Sarika
Rathaur, Sushma
Powiązania:
https://bibliotekanauki.pl/articles/1041437.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
actinomycin D
lymphatic filariasis
diethylcarbamazine
glutathione-S-transferase
Setaria cervi
Opis:
Glutathione-S-transferase (GST) a Phase-II drug detoxification enzyme, was detected in Setaria cervi, a bovine filarial parasite. In vitro effect of diethylcarbamazine, butylated hydroxyanisole and phenobarbitone on the GST of adult female S. cervi was assayed by the addition of these compounds in the maintenance medium. The specific activity of GST towards 1-chloro-2,4-dinitrobenzene was increased progressively 1.2-1.97, 1.3-2.4 and 1.2-2.7 times at 10-100 µM of diethylcarbamazine, butylated hydroxyanisole and phenobarbitone, respectively, after 5 h at 37°C. Substrate specificity studies showed a higher increase in specific activity with ethacrynic acid and no change with cumene hydroperoxide. Although the intensity of GST activity band was more in extract from diethylcarbamazine or butylated hydroxyanisole treated worms extract, an extra band of activity appeared in those worm extracts compared to control worm extract. SDS/PAGE showed increased thickness of the band corresponding to purified GST in extracts from diethylcarbamazine/butylated hydroxyanisole/phenobarbitone treated worms. Purification and quantification of GST from diethylcarbamazine and butylated hydroxyanisole treated worms indicated an increase in enzyme specific activity. The increase in GST protein by these agents was blocked by prior treatment with actinomycin D, indicative of a transcription dependent response. The role of this enzyme in motility and viability of microfilariae and adult female was tested in vitro using a range of known GST inhibitors. Of those tested, ethacrynic acid, ellagic acid, 1-chloro-2,4-dinitrobenzene, cibacron blue and butylated hydroxyanisole reduced the viability and motility of microfilariae and adult female worms at micromolar concentrations. These results suggest that S. cervi GST is inducible in response to the antifilarial drug diethylcarbamazine and may play an important role in parasite's survival, thus could be a potential drug target.
Źródło:
Acta Biochimica Polonica; 2005, 52, 2; 493-500
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Interleukin 18 (IL-18) as a target for immune intervention
Autorzy:
Wawrocki, Sebastian
Druszczynska, Magdalena
Kowalewicz-Kulbat, Magdalena
Rudnicka, Wieslawa
Powiązania:
https://bibliotekanauki.pl/articles/1038841.pdf
Data publikacji:
2016
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
interleukin-18 (IL-18)
IL-18 receptor
IL-18 binding protein
Opis:
Interleukin 18 (IL-18) is a pleiotropic cytokine involved in the regulation of innate and acquired immune response. In the milieu of IL-12 or IL-15, IL-18 is a potent inducer of IFN-gamma in natural killer (NK) cells and CD4 T helper (Th) 1 lymphocytes. However, IL-18 also modulates Th2 and Th17 cell responses, as well as the activity of CD8 cytotoxic cells and neutrophils, in a host microenvironment-dependent manner. It is produced by various hematopoietic and nonhematopoietic cells, including dendritic cells and macrophages. In an organism, bioactivity of the cytokine depends on the intensity of IL-18 production, the level of its natural inhibitory protein - IL-18BP (IL-18 binding protein) and the surface expression of IL-18 receptors (IL-18R) on the responding cells. This review summarizes the biology of the IL-18/IL-18BP/IL-18R system and its role in the host defense against infections. The prospects for IL-18 application in immunotherapeutic or prophylactic interventions in infectious and non-infectious diseases are discussed.
Źródło:
Acta Biochimica Polonica; 2016, 63, 1; 59-63
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.
Autorzy:
Barańczyk-Kuźma, Anna
Kuźma, Magdalena
Gutowicz, Marzena
Kaźmierczak, Beata
Sawicki, Jacek
Powiązania:
https://bibliotekanauki.pl/articles/1043346.pdf
Data publikacji:
2004
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
tricyclic antidepressants
human brain
glutathione S-transferase pi
Opis:
GST pi, the main glutathione S-transferase isoform present in the human brain, was isolated from various regions of the brain and the in vitro effect of tricyclic antidepressants on its activity was studied. The results indicated that amitripyline and doxepin - derivatives of dibenzcycloheptadiene, as well as imipramine and clomipramine - derivatives of dibenzazepine, inhibit the activity of GST pi from frontal and parietal cortex, hippocampus and brain stem. All these tricyclics are noncompetitive inhibitors of the enzyme with respect to reduced glutathione and noncompetitive (amitripyline, doxepin) or uncompetitive (imipramine, clomipramine) with respect to the electrophilic substrate. Their inhibitory effect is reversible and it depends on the chemical structure of the tricyclic antidepressants rather than on the brain localization of the enzyme. We conclude that the interaction between GST pi and the drugs may reduce their availability in the brain and thus affect their therapeutic activity. On the other hand, tricyclic antidepressants may decrease the efficiency of the enzymatic barrier formed by GST and increase the exposure of brain to toxic electrophiles. Reactive electrophiles not inactivated by GST may contribute in adverse effects caused by these drugs.
Źródło:
Acta Biochimica Polonica; 2004, 51, 1; 207-212
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Developmental changes in barley microRNA expression profiles coupled with miRNA target analysis
Autorzy:
Pacak, Andrzej
Kruszka, Katarzyna
Swida-Barteczka, Aleksandra
Nuc, Przemyslaw
Karlowski, Wojciech
Jarmolowski, Artur
Szweykowska-Kulinska, Zofia
Powiązania:
https://bibliotekanauki.pl/articles/1038742.pdf
Data publikacji:
2016
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
barley
microRNA
deep sequencing
development
Opis:
MicroRNAs are 19- to 24-nt-long single-stranded RNAs that are crucial regulators of gene expression which control plant development and response to environmental cues. We have analyzed microtranscriptomes of five barley developmental stages. Generally, during the barley development, miR168-3p and miR1432-5p levels increase while the 5'U-miR156-5p level decreases (with exception for the 2-week-old barley). We have identified two miR156-5p izomiRs (called 5'U-miR156-5p [20 nt] and 5'UU-miR156-5p [21 nt]), which were expressed differently during barley development. The 5' U-miR156-5p level decreased in 3-week-, 6-week-, and 68-day-old barley, when compared to the 1-week-old plants. Meanwhile, the 5' UU-miR156-5p level increased significantly in the 68-day-old barley plants. Moreover, only the 5' U-miR156 isomiR recognizes and guides unique transcription factor mRNAs from the Squamosa Promoter Binding Protein-Like (SPL) family. We identified many non-canonical microRNAs with changed expression levels during the barley development. Here, we present the profiles of microRNA expression characteristics for particular barley developmental stages. These analyses are accompanied by the experimental degradome analysis of miRNA targets.
Źródło:
Acta Biochimica Polonica; 2016, 63, 4; 799-809
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Advances with phospholipid signalling as a target for anticancer drug development
Autorzy:
Powis, Garth
Berggren, Margareta
Gallegos, Alfred
Frew, Timothy
Hill, Simon
Kozikowski, Alan
Bonjouklian, Rosanne
Zalkow, Leon
Abraham, Robert
Ashendel, Curtis
Schultz, Richard
Merriman, Ronald
Powiązania:
https://bibliotekanauki.pl/articles/1045198.pdf
Data publikacji:
1995
Wydawca:
Polskie Towarzystwo Biochemiczne
Źródło:
Acta Biochimica Polonica; 1995, 42, 4; 395-403
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Glucosamine-6-phosphate synthase, a novel target for antifungal agents. Molecular modelling studies in drug design.
Autorzy:
Wojciechowski, Marek
Milewski, Sławomir
Mazerski, Jan
Borowski, Edward
Powiązania:
https://bibliotekanauki.pl/articles/1041368.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
drug design
glucosamine-6-phosphate synthase
fungal infections
glutamine amidotransferases
molecular modelling
Opis:
Fungal infections are a growing problem in contemporary medicine, yet only a few antifungal agents are used in clinical practice. In our laboratory we proposed the enzyme L-glutamine : D-fructose-6-phosphate amidotransferase (EC 2.6.1.16) as a new target for antifungals. The structure of this enzyme consists of two domains, N-terminal and C-terminal ones, catalysing glutamine hydrolysis and sugar-phosphate isomerisation, respectively. In our laboratory a series of potent selective inhibitors of GlcN-6-P synthase have been designed and synthesised. One group of these compounds, including the most studied N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP), behave like glutamine analogs acting as active-site-directed inactivators, blocking the N-terminal, glutamine-binding domain of the enzyme. The second group of GlcN-6-P synthase inhibitors mimic the transition state of the reaction taking place in the C-terminal sugar isomerising domain. Surprisingly, in spite of the fact that glutamine is the source of nitrogen for a number of enzymes it turned out that the glutamine analogue FMDP and its derivatives are selective against GlcN-6-P synthase and they do not block other enzymes, even belonging to the same family of glutamine amidotransferases. Our molecular modelling studies of this phenomenon revealed that even within the family of related enzymes substantial differences may exist in the geometry of the active site. In the case of the glutamine amidotransferase family the glutamine binding site of GlcN-6-P synthase fits a different region of the glutamine conformational space than other amidotransferases. Detailed analysis of the interaction pattern for the best known, so far, inhibitor of the sugar isomerising domain, namely 2-amino-2-deoxy-d-glucitol-6-phosphate (ADGP), allowed us to suggest changes in the structure of the inhibitor that should improve the interaction pattern. The novel ligand was designed and synthesised. Biological experiments confirmed our predictions. The new compound named ADMP is a much better inhibitor of glucosamine-6-phosphate synthase than ADGP.
Źródło:
Acta Biochimica Polonica; 2005, 52, 3; 647-653
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Wyświetlanie 1-15 z 21

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