Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi

Kandeel, Mahmoud; Al‐Taher, Abdulla

doi:10.1007/s11250-020-02366-8

Cited by 3 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ideal target is present in the parasite and absent in the host. Recently, we have introduced several new antimicrobial targets, which were investigated using bioinformatics tools to elucidate the differences between the host and microbial proteins (Kandeel & Kitade, 2011a, 2011bKato et al, 2012;Noguchi et al, 2013;Kandeel et al, 2020;Kandeel & Al-Taher, 2020a, 2020b, 2021. In this context, pyrimidine enzymes are indispensable for life due to their role in nucleic acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

2021

View full text Add to dashboard Cite

Decoding camel (Camelus genus) genome sequences (Jirimutu et al., 2012) will accelerate drug discovery studies against camel pathogens. One specific line of inquiry is investigating pyrimidine metabolic pathways, and finding unique differences in structure, function, sequence, or phylogeny associated with these pathways could contribute to identifying new drug targets. KEGG maps have been used (Ogata et al., 1998;Kanehisa et al., 2007;Kanehisa et al., 2016) to compare the enzymes involved in thymidine metabolism pathways in camels and T. evansi.In this work, comprehensive bioinformatic tools were used to investigate enzyme sequences in camels and T. evansi and compare their domains and motif content, searching for similar proteins and identifying their phylogenetic relationships. We plotted the pathway of thymidine metabolism in the two organisms, providing bioinformatics evidence of unique differences between camels and T. evansi that could be exploited for future drug discovery processes. MATERIALS AND METHODS Construction of the metabolic mapThe Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to retrieve the thymidine pathway maps.The map was accessed at the following link (https:// www.genome.jp/kegg-bin/show_pathway?map00240). The structure of nucleotides and the pathways were written by ChemDraw software (Figure 1). Retrieval of protein sequencesThe NCBI protein database was used to obtain the sequences of camel enzymes (http://www.ncbi.nlm.nih.gov/protein), and the T. evansi protein sequences were retrieved from the Kinetoplastom genome project (http://tritrypdb.org/tritrypdb). The sequence files in FASTA format were stored and processed by multiple software programs, including the CLC main workbench, Geneious, and Genedoc. The accession numbers of the retrieved sequences are provided in Figures 2-5. Basic local alignment search tool (BLAST)A BLAST search was performed using the NCBI search engine (Madden, 2013). The BLAST tool was used to find orthologues with high similarity to the retrieved sequences by searching a database of non-redundant (nr) protein sequences using the default settings. The retrieved camel and T. evansi sequences were input into the protein BLAST server at ( h t t p s : / / b l a s t . n c b i . n l m . n i h . g o v / B l a s t . c g i ? P R O G R A M =blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome) using the FASTA sequences and searching the nr protein

show abstract

Section: Discussionmentioning

confidence: 99%

Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

2021

View full text Add to dashboard Cite

show abstract

“…For docking studies, three-dimensional structures of anti-apoptotic proteins, such as BCL-2 and CASPASE-3, were retrieved from the RCSB PDB protein data bank [ 57 , 58 ], with their respective PDB ID (4LVT and 3DEK). For docking simulations, water molecules and free hydrogen atoms were removed, and polar molecules were added to all protein structures using the pymol tool and automated AutoDock tool.…”

Section: Methodsmentioning

confidence: 99%

Insight into Analysis of Essential Oil from Anisosciadium lanatum Boiss.—Chemical Composition, Molecular Docking, and Mitigation of Hepg2 Cancer Cells through Apoptotic Markers

Khalil

Ibrahim

Darrag

et al. 2021

Plants

View full text Add to dashboard Cite

Essential oils have been used in various traditional healing systems since ancient times worldwide, due to their diverse biological activities. Several studies have demonstrated their plethora of biological activities—including anti-cancer activity—in a number of cell lines. Anisosciadium lanatum Boiss. is a perennial aromatic herb. Traditionally, it is an edible safe herb with few studies exploring its importance. The current study aims to investigate the chemical composition of essential oil isolated from Anisosciadium lanatum using GC-MS, as well as report its anti-cancer potential and its mechanistic effect on HepG2 liver cancer cell lines, and conduct molecular docking studies. To achieve this, the essential oil was isolated using a Clevenger apparatus and analyzed using GC-MS. The cell viability of HepG2 liver cancer and normal fibroblast NIH-3T3 cell lines was assessed by MTT cytotoxicity assay. The effects of the essential oil on cell migration and invasion were assessed using wound healing and matrigel assays, respectively. The effect of the essential oil on migration and apoptotic-regulating mRNA and proteins was quantified using quantitative real-time PCR and Western blot techniques, respectively. Finally, computational docking tools were used to analyze in silico binding of major constituents from the essential oil against apoptotic and migration markers. A total of 38 components were identified and quantified. The essential oil demonstrated regulation of cell proliferation and cell viability in HepG2 liver cancer cells at a sub-lethal dose of 10 to 25 μg/mL, and expressed reductions of migration and invasion. The treatment with essential oil indicated mitigation of cancer activity by aborting the mRNA of pro-apoptotic markers such as BCL-2, CASPASE-3, CYP-1A1, and NFκB. The algorithm-based binding studies demonstrated that eucalyptol, nerol, camphor, and linalool have potent binding towards the anti-apoptotic protein BCL-2. On the other hand, camphor and eucalyptol showed potent binding towards the pro-apoptotic protein CASPASE-3. These findings highlight the effectiveness of the essential oil isolated from Anisosciadium lanatum to drive alleviation of HepG2 cancer cell progression by modulating apoptotic markers. Our findings suggest that Anisosciadium lanatum could be used as a phytotherapeutic anti-cancer agent, acting through the regulation of apoptotic markers. More well-designed in vivo trials are needed in order to verify the obtained results.

show abstract

The Impact of Developmental and Metabolic Cues on Cytoophidium Formation

Zhang,

Liu

2024

IJMS

View full text Add to dashboard Cite

The cytoophidium, composed mainly of CTP synthase (CTPS), is a newly discovered dynamic filamentous structure in various organisms such as archaea, bacteria, and humans. These filamentous structures represent a fascinating example of intracellular compartmentation and dynamic regulation of metabolic enzymes. Currently, cytoophidia have been proven to be tightly regulated and highly dynamic, responding rapidly to developmental and metabolic cues and playing a critical role in maintaining cellular homeostasis. In this review, we would like to discuss in detail the characteristics, mechanisms, functions, and potential applications of this conservative but promising organelle.

show abstract

Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi

Cited by 3 publications

References 26 publications

Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

Insight into Analysis of Essential Oil from Anisosciadium lanatum Boiss.—Chemical Composition, Molecular Docking, and Mitigation of Hepg2 Cancer Cells through Apoptotic Markers

The Impact of Developmental and Metabolic Cues on Cytoophidium Formation

Contact Info

Product

Resources

About