Department Of Botany

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Subject: search.filters.subject.Molecular docking

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Now showing 1 - 7 of 7
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    Molecular characterization and differential expression of an aromatic heptaketide producing type III plant polyketide synthase from Himalayan rhubarb
    (Springer, 2022-01-15T00:00:00) Pandith, Shahzad A.; Dhar, Niha; Bhosale, Sumedha; Barvkar, Vitthal T.; Razdan, Sumeer; Shah, Manzoor A.; Lattoo, Surrinder K.
    Rheum australe (Himalayan Rhubarb, Polygonaceae), an endangered medicinal and vegetable herb owes its age-old remedying properties to the bio-active phyto-constituents viz. anthraquinones, stilbenoids, chromones and dietary flavonoids. Polyketide pathway primarily involving the intricate Type III polyketide synthases (PKSs) contributes to the biosynthesis of these phyto-constituents. In the present study, we perform a homology-based approach to isolate an 1176�bp full-length cds sequence of the RaALS gene showing an equitable level of sequence similarity to related Type III PKSs at both nucleic acid and amino acid levels. In silico characterization revealed the presence of highly conserved amino acid residues found in nearly all Type III PKSs including the conserved active-site residues, signature motif and cyclization pocket residues with an exception of Ile256 and Gly258. Docking studies established major interactions between the starter acetyl-CoA and RaALS. Copy number analysis suggested slender evolution in Type III PKS in R. australe having a single copy of RaALS gene. qRT-PCR analyses revealed corroboration between the higher expression of RaALS in leaves followed by stem and root with that of the metabolite concentration. Expression studies further showed a direct increase of RaALS transcripts with the growing metabolite accretion in relation to altitude suggesting a probable involvement of specific Type III PKS in biosynthesis of the major phyto-constituents. Furthermore, abiotic stressors viz. methyl jasmonate, salicylic acid and UV light enhanced RaALS transcription hinting towards its role in defense mechanism in R. australe and highlighting the significance of RaALS as a prospective target for metabolic engineering. � 2022, Korean Society for Plant Biotechnology.
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    Carotenoid cleavage dioxygenases (HD-CCD1A and B) contribute as strong negative regulators of ?-carotene in Indian bread wheat (cv. HD2967)
    (Springer Science and Business Media Deutschland GmbH, 2021-04-16T00:00:00) Thakur, Nandita; Flowerika; Thakur, Neha; Khan, Shahirina; Pandey, Ajay K.; Tiwari, Siddharth
    Wheat (Triticum aestivum L.) is the most common cereal crop that is considered to be deficient in provitamin A carotenoids. Carotenoids are prone to degrade into apocarotenoids by the activity of carotenoid cleavage dioxygenases (CCDs). Hence, in this study, multiple CCDs were cloned from commercial Indian wheat cultivar HD2967 to understand their role in provitamin A carotenoids degradation. The homoeolog specific expression of HD-CCD1 and HD-CCD4 at different grain filling stages revealed the higher expression of transcripts arising from the A and B subgenomes of HD-CCD1. Furthermore, the grain development stages showed a strong negative correlation of HD-CCD1A (r = ? 0.969) and B (r = ? 0.970) homoeologs expression to that of ?-carotene accumulation. It suggested that they could be potentially involved in deciding the turn-over of ?-carotene in wheat grain. Three-dimensional (3D) structures for all six homoeologs of HD-CCD1 and HD-CCD4 were predicted using maize VP14 template to gain better insight into their molecular mechanism. Ramachandran plot assessment revealed that ~ 90% of residues are in the most favoured region. Docking studies with various carotenoid substrates revealed the higher affinity of HD-CCD1A and B for ?-carotene and ?-cryptoxanthin. Bacterial complementation analysis validated the functional role of all six homoeologs with HD-CCD1B showing the highest activity followed by HD-CCD1A for ?-carotene degradation. Results of this study provide valuable insights into the characteristics of HD-CCDs in wheat and thereby justifying them (HD-CCD1A and B) as the candidate genes for employing genome editing tools for developing ?-carotene enriched wheat grains. � 2021, King Abdulaziz City for Science and Technology.
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    Molecular characterization and differential expression of an aromatic heptaketide producing type III plant polyketide synthase from Himalayan rhubarb
    (Springer, 2022-01-15T00:00:00) Pandith, Shahzad A.; Dhar, Niha; Bhosale, Sumedha; Barvkar, Vitthal T.; Razdan, Sumeer; Shah, Manzoor A.; Lattoo, Surrinder K.
    Rheum australe (Himalayan Rhubarb, Polygonaceae), an endangered medicinal and vegetable herb owes its age-old remedying properties to the bio-active phyto-constituents viz. anthraquinones, stilbenoids, chromones and dietary flavonoids. Polyketide pathway primarily involving the intricate Type III polyketide synthases (PKSs) contributes to the biosynthesis of these phyto-constituents. In the present study, we perform a homology-based approach to isolate an 1176�bp full-length cds sequence of the RaALS gene showing an equitable level of sequence similarity to related Type III PKSs at both nucleic acid and amino acid levels. In silico characterization revealed the presence of highly conserved amino acid residues found in nearly all Type III PKSs including the conserved active-site residues, signature motif and cyclization pocket residues with an exception of Ile256 and Gly258. Docking studies established major interactions between the starter acetyl-CoA and RaALS. Copy number analysis suggested slender evolution in Type III PKS in R. australe having a single copy of RaALS gene. qRT-PCR analyses revealed corroboration between the higher expression of RaALS in leaves followed by stem and root with that of the metabolite concentration. Expression studies further showed a direct increase of RaALS transcripts with the growing metabolite accretion in relation to altitude suggesting a probable involvement of specific Type III PKS in biosynthesis of the major phyto-constituents. Furthermore, abiotic stressors viz. methyl jasmonate, salicylic acid and UV light enhanced RaALS transcription hinting towards its role in defense mechanism in R. australe and highlighting the significance of RaALS as a prospective target for metabolic engineering. � 2022, Korean Society for Plant Biotechnology.
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    Carotenoid cleavage dioxygenases (HD-CCD1A and B) contribute as strong negative regulators of ?-carotene in Indian bread wheat (cv. HD2967)
    (Springer Science and Business Media Deutschland GmbH, 2021-04-16T00:00:00) Thakur, Nandita; Flowerika; Thakur, Neha; Khan, Shahirina; Pandey, Ajay K.; Tiwari, Siddharth
    Wheat (Triticum aestivum L.) is the most common cereal crop that is considered to be deficient in provitamin A carotenoids. Carotenoids are prone to degrade into apocarotenoids by the activity of carotenoid cleavage dioxygenases (CCDs). Hence, in this study, multiple CCDs were cloned from commercial Indian wheat cultivar HD2967 to understand their role in provitamin A carotenoids degradation. The homoeolog specific expression of HD-CCD1 and HD-CCD4 at different grain filling stages revealed the higher expression of transcripts arising from the A and B subgenomes of HD-CCD1. Furthermore, the grain development stages showed a strong negative correlation of HD-CCD1A (r = ? 0.969) and B (r = ? 0.970) homoeologs expression to that of ?-carotene accumulation. It suggested that they could be potentially involved in deciding the turn-over of ?-carotene in wheat grain. Three-dimensional (3D) structures for all six homoeologs of HD-CCD1 and HD-CCD4 were predicted using maize VP14 template to gain better insight into their molecular mechanism. Ramachandran plot assessment revealed that ~ 90% of residues are in the most favoured region. Docking studies with various carotenoid substrates revealed the higher affinity of HD-CCD1A and B for ?-carotene and ?-cryptoxanthin. Bacterial complementation analysis validated the functional role of all six homoeologs with HD-CCD1B showing the highest activity followed by HD-CCD1A for ?-carotene degradation. Results of this study provide valuable insights into the characteristics of HD-CCDs in wheat and thereby justifying them (HD-CCD1A and B) as the candidate genes for employing genome editing tools for developing ?-carotene enriched wheat grains. � 2021, King Abdulaziz City for Science and Technology.
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    In silico screening and molecular interaction studies of tetrahydrocannabinol and its derivatives with acetylcholine binding protein
    (Bentham Science Publishers B.V., 2018) Panigrahi, P.P.; Singla, Ramit; Bansal, A.; Comar, Junior M.; Jaitak, Vikas; Yennamalli, R.M; Singh, T.R.
    Background: Alzheimer’s disease (AD) is the fourth largest cause of death among people over 65 years of age. Accumulation of β-amyloid and cholinergic deficiency are two prominent pathological descriptions for AD. Objective: Depletion of acetylcholine at the site of its action is thought to be the prime cause of AD. It has been reported that tetrahydrocannabinol (THC) exhibits anticholinesterase activity and it has been proposed as a suitable candidate for treating neurological disorders such as AD. Methods: Using an in silico approach, including virtual screening, THC and its derivatives were docked against acetylcholine binding protein (AChBP) using AutoDock. The top-ranked molecules were studied in detail using an induced fit docking approach followed by characterization of their binding affinity, toxicity and ADME properties using TOPKAT and QikProp. Results: THC_JUIT25, a novel derivative of THC, showed maximum binding affinity and was observed as a promising candidate for performing receptor-ligand interaction studies using molecular dynamics simulation. Conclusion: In this study, we propose a novel THC derivative as a potential lead molecule in the drug development strategy for treating AD.
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    In Silico and In Vitro Studies Evidenced Anticancer Natural Compounds, a Targeting Chemokine Receptor
    (iMedPub, 2016) Singh, Pushpendra; Bast, Felix
    Chemokines are a family of small chemotactic cytokines, which play a significant role in lymphocyte homing to secondary lymphoid organs in addition to tumor growth and metastasis. Thus, inhibition of chemokine receptor caught attention for anticancer treatment strategy. We studied molecular docking of chemokines receptor CXCR2, CXCR4, and CCR5 against natural and marine compounds. All selected natural and marine compounds were docked with the X-ray crystal structure of CXCR2, CXCR4, and CCR5 retrieved from the PDB by using Maestro 9.6. Molecular docking was executed by the XP (extra precision) mode of GLIDE. On the basis of Gscore and protein-ligand interactions, top-ranking compounds were outlined. The docking study carried out to summarize the various Gscore, hydrophobic, electrostatic bond, hydrogen bond, π-cation and π-π interactions and oversee the protein-ligand interactions. Moreover, effect of Epigallocatechin-3-gallate (EGCG) on biological activity such as mRNA expression (CXCR2, CCR5, and Bid), cell proliferation, ROS, and cell-migration was reported after the 48 hrs treatments in MCF-7 cells. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of CXCR2, CCR5 and increased the Bid at 40 μM and 80 μM concentration. Moreover, EGCG significantly reduced cell proliferation, ROS generation and cell-migration after 48 hours treatments.
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    Natural Compounds Targeting Transforming Growth Factor-β: In Silico and In Vitro Study
    (ejBio, 2016) Singh, Pushpendra; Bast, Felix; Singh, Ravi Shankar
    Inhibition of the tumor-promoting effects of transforming growth factor beta receptor (TGFβR) in carcinogenesis provides a better therapeutic intervention. Various natural compounds, inhibitors of TGFβR have been used for in vitro and in vivo anticancer study. Although very few TGFβR inhibitors are now intensifying in preclinical studies. In this study our aim to investigate TGFβR1, TGFβR2 and TAK1 inhibitor by using molecular docking and in vitro study. Our result revealed that some compounds have better docking energy. Moreover, the effect of two lead molecules epigallocatechin gallate (EGCG) and myricetin on the mRNA expression of TGFβR1 was reported after the 48 hrs treatments in HepG2 and PC3 cancer cell lines. The RT-PCR showed that compound EGCG and myricetin reduced the mRNA expression of TGFβR1 at 80 μM concentration. This molecular docking study provides a better understanding of binding of compounds to the active site of proteins and to summarize the various binding energy, hydrophobic, hydrogen, an electrostatic bond that are decisive for the protein-ligand interactions. Further experimental work will be required for validation of our results.