Insilico docking study of compounds elucidated from helicteres isora fruits with ampkinase- insulin receptor

Insulin receptor (IR) proteins were essential intracellular signaling peptides in the insulin action cascade. Insulin receptor substrate proteins (IRS-1and IRS-2) serve and regulate the insulin level in the normal insulin action. The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing. Such type of proteins were cyclic adenosine monophosphate-activated protein kinase, this proteins play a key role in the insulin response and regulation. Type -2 Diabetes mellitus occurs during prolonged periods of peripheral insulin resistance due to inactivation of IRS proteins. The compounds isolated from the medicinal plants were safer than synthetic drugs and possess high bio activity. In the present study, four compounds were elucidated from fruits of Helicteres isora. The elucidated compounds were evaluated for the antidiabetic activity using in silico docking study. The receptor was analyzed for the active site and pocket finder tools. The aminoacids such as Phenylalanine, Lysine, Glutamic acid and Asparigine were predicted as active site binding residues. Docking studies were done through Autodock 4 software. All the compounds from fruits of Helicteres isora showed good docking profiles with AMP Kinase, except compound-3 (1,2,3,4-tetrahydro-1,5,6,8-tetramethyl-7-(2-methylprop-1-enylnaphthalene-4-ylpivalate). Finally the result from the study demonstrates that the HS-1, HS-2 and HS-4 posses potent anti diabetic activity against type-2 diabetes mellitus through drug action on AMP kinase cascade system.     

CNDO calculations on the conformational structure of acetylcholine

Molecular orbital theory in the CNDO framework has been used to calculate the torsional angles which lead to minimum energy conformations in acetylcholine. The calculated angles agree well with the experimental observations on acetylcholine and its derivatives. The results have been compared with the earlier predictions based on extended Hückel theory and van der Waal pairwise interactions.     

Convergent donor and acceptor substrate utilization among kinase ribozymes

Accommodation of donor and acceptor substrates is critical to the catalysis of (thio)phosphoryl group transfer, but there has been no systematic study of donor nucleotide recognition by kinase ribozymes, and there is relatively little known about the structural requirements for phosphorylating internal 2′OH. To address these questions, new self-phosphorylating ribozymes were selected that utilize ATP(gammaS) or GTP(gammaS) for 2′OH (thio)phosphorylation. Eight independent sequence families were identified among 57 sequenced isolates. Kinetics, donor nucleotide recognition and secondary structures were analyzed for representatives from each family. Each ribozyme was highly specific for its cognate donor. Competition assays with nucleotide analogs showed a remarkable convergence of donor recognition requirements, with critical contributions to recognition provided by the Watson–Crick face of the nucleobase, lesser contributions from donor nucleotide ribose hydroxyls, and little or no contribution from the Hoogsteen face. Importantly, most ribozymes showed evidence of significant interaction with one or more donor phosphates, suggesting that—unlike most aptamers—these ribozymes use phosphate interactions to orient the gamma phosphate within the active site for in-line displacement. All but one of the mapped (thio)phosphorylation sites are on unpaired guanosines within internal bulges. Comparative structural analysis identified three loosely-defined consensus structural motifs for kinase ribozyme active sites.     

Statistical optimization of medium components and growth conditions by response surface methodology to enhance lipase production by Aspergillus carneus

A response surface approach has been used to study the production of an extracellular lipase from Aspergillus carneus, which has the property of immense industrial importance. Interactions were studied for five different variables (sunflower oil, glucose, peptone, agitation rate and incubation period), which were found influential for lipase production by one-at a time method. We report a 1.8-fold increase in production, with the final yield of 12.7 IU/ml in comparison to 7.2 U/ml obtained by one-at-a-time method. Using the statistical approach (response surface methodology (RSM)) the optimum values of these most influential parameters were as follows: sunflower oil (1%), glucose (0.8%), peptone (0.8%), agitation rate (200 rpm) and incubation period (96 h) at 37 °C. The subsequent verification experiment confirmed the validity of the model.     

Microvesicles promote megakaryopoiesis by regulating DNA methyltransferase and methylation of Notch1 promoter

Megakaryopoiesis is the process of formation of mature megakaryocytes that takes place in the bone marrow niche resulting in the release of platelets into the peripheral blood. It has been suggested that cell to cell communication in this dense bone marrow niche may influence the fate of the cells. Numerous studies point to the role of exosomes and microvesicles not only as a messenger of the cellular crosstalk but also in growth and developmental process of various cell types. In the current study, we explored the effects of megakaryocyte-derived microvesicles in hematopoietic cell lines in the context of differentiation. Our study demonstrated that microvesicles isolated from the induced megakaryocytic cell lines have the ability to stimulate noninduced cells specifically into that particular lineage. We showed that this lineage commencement comes from the change in the methylation status of Notch1 promoter, which is regulated by DNA methyltransferases.