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71.
Parthiban Marimuthu ByungHoon Kim Seong S. Seo 《Journal of biomolecular structure & dynamics》2019,37(2):307-320
Organophosphate compounds (OPC) have become the primary choice as insecticides and are widely used across the world. Additionally, OPCs were also commonly used as a chemical warfare agent that triggers a great challenge to public safety. Exposure of OPCs to human causes immediate excitation of cholinergic neurotransmission through transient elevation of synaptic acetylcholine (ACh) levels and accumulations. Likewise, prolonged exposure of OPCs can affect the processes in immune response, carbohydrate metabolism, cardiovascular toxicity, and several others. Studies revealed that the toxicity of OPCs was provoked by inhibition of acetylcholinesterase (AChE). Therefore, combined in silico approaches – pharmacophore-based 3D-QSAR model; docking and Molecular Dynamics (MD) – were used to assess the precise and comprehensive effects of series of known OP-derived compounds together with its ?log LD50 values. The selected five-featured pharmacophore model – AAHHR.61 – displayed the highest correlation (R2 = .9166), cross-validated coefficient (Q2 = .8221), F = 63.2, Pearson-R = .9615 with low RMSE = .2621 values obtained using five component PLS factors. Subsequently, the well-validated model was then used as a 3D query to search novel OPCs using a high-throughput virtual screening technique. Simultaneously, the docking studies predicted the binding pose of the most active OPC in the MdAChE binding pocket. Additionally, the stability of docking was verified using MD simulation. The results revealed that OP22 and predicted lead compounds bound tightly to S315 of MdAChE through potential hydrogen bond interaction over time. Overall, this study might provide valuable insight into binding mode of OPCs and hit compounds to inhibit AChE in housefly. 相似文献
72.
Tara Ann Burns Marimuthu Subathra Paola Signorelli Young Choi Xiaofeng Yang Yong Wang Maristella Villani Kapil Bhalla Daohong Zhou Chiara Luberto 《Journal of lipid research》2013,54(3):794-805
Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (CML) cells. The increased SMS in K562 cells was caused by the presence of Bcr-abl, a hallmark of CML; stable expression of Bcr-abl elevated SMS activity in HL-60 cells while inhibition of the tyrosine kinase activity of Bcr-abl with Imatinib mesylate decreased SMS activity in K562 cells. The increased SMS activity was the result of up-regulation of the Sms1 isoform. Inhibition of SMS activity with D609 (a pharmacological SMS inhibitor) or down-regulation of SMS1 expression by siRNA selectively inhibited the proliferation of Bcr-abl-positive cells. The inhibition was associated with an increased production of ceramide and a decreased production of DAG, conditions that antagonize cell proliferation. A similar change in lipid profile was also observed upon pharmacological inhibition of Bcr-abl (K526 cells) and siRNA-mediated down-regulation of BCR-ABL (HL-60/Bcr-abl cells). These findings indicate that Sms1 is a downstream target of Bcr-abl, involved in sustaining cell proliferation of Bcr-abl-positive cells. 相似文献
73.
In order to investigate the modes of inheritance of serum immunoglobulin E (IgE) levels and atopic disease, serum IgE levels and data on allergic disease were obtained from 42 families ascertained through asthmatic children visiting an allergy clinic. Although the mean IgE levels were elevated (mean 637 U/ml), the prevalence of atopic disease in this population was surprisingly low. When the data were analyzed using complex segregation analysis, no major locus could be detected. Moreover, the polygenic heritability was unexpectedly small even though the correlation between serum IgE levels and the liability to atopic disease was around 0.4. Given this unusual set of findings, it is postulated that parasitic infections in this population have (in accordance with well-established results of parasitic disease) caused both elevated levels of serum IgE and a decreased prevalence of allergic disease with the possible masking of the various genetic components of serum IgE levels and atopic disease. 相似文献
74.
Priyadharshini Ramachandran Marimuthu Jeya Hee-Jung Moon Kyoung-Mi Lee In-Won Kim Jung-Hoe Kim Jung-Kul Lee 《Biotechnology letters》2010,32(7):891-895
Methylan polysaccharide derivatives were prepared by dialkylaminoalkylation and reductive amination followed by quaternization. Their antitumor activity was investigated and a relationship between structure and activity is suggested. For quaternized DEAE-methylan at only 75 μg ml?1, tumor cell proliferation was suppressed by 58–84% in three cell lines tested in the order Colo < Hela < HepG2. 相似文献
75.
Jesu Arockiaraj Rajesh Palanisamy Venkatesh Kumaresan Prasanth Bhatt Mukesh Kumar Chaurasia Marimuthu Kasi Mukesh Pasupuleti Annie J. Gnanam 《Biologia》2014,69(8):1065-1078
We report a molecular characterization of S1 family serine protease (SP-1) from snakehead murrel (or called striped murrel) Channa striatus (Cs). CsSP-1 polypeptide contained a catalytic core domain (otherwise known as serine protease trypsin domain) between H20 and I237 along with a catalytic triad at H61, D104 and S197. Phylogenetic analysis confirmed that CsSP-1 belongs to serine protease S1 family. The tertiary structure showed that CsSP-1 contains 14 β-sheets as 2 separate β-barrels (the first β-barrel consists of 8 β-sheets in the N-terminal region and the second β-barrel consists of 6 β-sheets in the C-terminal region) and 3 α-helical regions. Significantly (P < 0.05) the highest CsSP-1 mRNA expression was observed in intestine, liver and kidney, moderate expression was seen in spleen, head kidney, skin and blood, and the lowest one in brain, gill, muscle and heart. Further, the expression was induced in intestine with fungus Aphanomyces invadans and bacteria Aeromonas hydrophila. The recombinant CsSP-1 protein showed antibacterial activity against both gram-negative and gram-positive bacteria. The optimum CsSP-1 enzyme activity against the substrate casein was determined at 8 mM casein concentration. Moreover, the activity was highly influenced by 5 mM phenyl-methylsulfonyl fluoride followed by ethylenediaminetetraacetic acid, 4-(2-aminoethyl)benzenesulfonylfluoride hydrochloride and calpain inhibitor I. The CsSP-1 enzyme exhibited the highest activity at pH 7.5 and temperature 35°C. The overall results showed the potential involvement of CsSP-1 in the immune system of murrels. However, further research is necessary to study the mechanism of implicit trypsin association in the defence process. 相似文献
76.
77.
Ahsan H Khandoker Herbert F Jelinek Marimuthu Palaniswami 《Biomedical engineering online》2009,8(1):3-12
Background
Cardiac autonomic neuropathy (CAN) in diabetes has been called a "silent killer", because so few patients realize that they suffer from it, and yet its effect can be lethal. Early sub clinical detection of CAN and intervention are of prime importance for risk stratification in preventing sudden death due to silent myocardial infarction. This study presents the usefulness of heart rate variability (HRV) and complexity analyses from short term ECG recordings as a screening tool for CAN. 相似文献78.
Marimuthu Jeya Hee-Jung Moon Jeong-Lim Lee In-Won Kim Jung-Kul Lee 《Applied microbiology and biotechnology》2010,85(6):1653-1663
Coenzyme Q10 (CoQ10), an obligatory cofactor in the aerobic respiratory electron transfer for energy generation, is formed from the conjugation
of a benzoquinone ring with a hydrophobic isoprenoid chain. CoQ10 is now used as a nutritional supplement because of its antioxidant properties and is beneficial in the treatment of several
human diseases when administered orally. Bioprocesses have been developed for the commercial production of CoQ10 because of its increased demand, and these bioprocesses depend on microbes that produce high levels of CoQ10 naturally. However, as knowledge of the biosynthetic enzymes and the regulatory mechanisms modulating CoQ10 production increases, approaches arise for the genetic engineering of CoQ10 production in Escherichia coli and Agrobacterium tumefaciens. This review focused on approaches for CoQ10 production, strategies used to engineer CoQ10 production in microbes, and potential applications of CoQ10. 相似文献
79.
Jin-Ha Kim Ponnandy Prabhu Marimuthu Jeya Manish Kumar Tiwari Hee-Jung Moon Raushan Kumar Singh Jung-Kul Lee 《Applied microbiology and biotechnology》2010,85(6):1839-1847
An isolated gene from Bacillus subtilis str. 168 encoding a putative isomerase was proposed as an L-arabinose isomerase (L-AI), cloned into Escherichia coli, and its nucleotide sequence was determined. DNA sequence analysis revealed an open reading frame of 1,491 bp, capable of
encoding a polypeptide of 496 amino acid residues. The gene was overexpressed in E. coli and the protein was purified using nickel-nitrilotriacetic acid chromatography. The purified enzyme showed the highest catalytic
efficiency ever reported, with a k
cat of 14,504 min−1 and a k
cat/K
m of 121 min−1 mM−1 for L-arabinose. A homology model of B. subtilis L-AI was constructed based on the X-ray crystal structure of E. coli
L-AI. Molecular dynamics simulation studies of the enzyme with the natural substrate, L-arabinose, and an analogue, D-galactose, shed light on the unique substrate specificity displayed by B. subtilis
L-AI only towards L-arabinose. Although L-AIs have been characterized from several other sources, B. subtilis
L-AI is distinguished from other L-AIs by its high substrate specificity and catalytic efficiency for L-arabinose. 相似文献
80.
Manish Kumar Tiwari Hee-Jung Moon Marimuthu Jeya Jung-Kul Lee 《Applied microbiology and biotechnology》2010,87(2):571-581
An NAD+-dependent xylitol dehydrogenase from Rhizobium etli CFN42 (ReXDH) was cloned and overexpressed in Escherichia coli. The DNA sequence analysis revealed an open reading frame of 1,044 bp, capable of encoding a polypeptide of 347 amino acid
residues with a calculated molecular mass of 35,858 Da. The ReXDH protein was purified as an active soluble form using GST
affinity chromatography. The molecular mass of the purified enzyme was estimated to be ∼34 kDa by sodium dodecyl sulfate–polyacrylamide
gel and ∼135 kDa with gel filtration chromatography, suggesting that the enzyme is a homotetramer. Among various polyols,
xylitol was the preferred substrate of ReXDH with a K
m = 17.9 mM and kcat
/K
m = 0.5 mM−1 s−1 for xylitol. The enzyme had an optimal pH and temperature of 9.5 and 70 °C, respectively. Heat inactivation studies revealed
a half life of the ReXDH at 40 °C of 120 min and a half denaturation temperature (T
1/2) of 53.1 °C. ReXDH showed the highest optimum temperature and thermal stability among the known XDHs. Homology modeling and
sequence analysis of ReXDH shed light on the factors contributing to the high thermostability of ReXDH. Although XDHs have
been characterized from several other sources, ReXDH is distinguished from other XDHs by its high thermostability. 相似文献