Adenylyl cyclase 2 (AC2) is one of nine membrane-bound isoforms of adenylyl cyclase that converts ATP into cyclic AMP (cAMP), an important second messenger molecule. Upregulation of AC2 is linked to cancers like pancreatic and small intestinal neuroendocrine tumors (NETs). The structures of the various isoforms of adenylyl cyclases are highly homologous, posing a significant challenge to drug discovery efforts for an effective, isoform-selective modulator of AC2. In a previous study, a screen identified a potential isoform-selective and noncompetitive inhibitor of AC2, SKF83566. In the present study, molecular modeling is used to explore the mode of inhibition of AC2 by SKF83566 and to investigate the active enantiomer of SKF83566. Homology models of hAC2 were built based on canine AC5-C1a and rat AC2-C2a templates. With these models, a combination of flexible docking, molecular dynamics simulations, and free energy calculations using the MM/GBSA methodology suggested an allosteric mechanism in which (S)-SKF83566 binds to an allosteric site near ATP and alters the protein conformation of the ATP binding site, potentially preventing the adenosine moiety of ATP from forming an archlike shape to form cAMP. The predicted binding preference for the (S)-SKF83566 enantiomer and the predicted free energy are consistent with the experimental data.

Assembly of the peptidoglycan is crucial in maintaining viability of bacteria and in defining bacterial cell shapes, both of which are important for existence in the ecological niche that the organism occupies. Here, eight crystal structures for a member of the cell-shapedetermining class of Campylobacter jejuni, the peptidoglycan peptidase 3 (Pgp3), are reported. Characterization of the turnover chemistry of Pgp3 reveals cell wall D,D-endopeptidase and D,D-carboxypeptidase activities. Catalysis is accompanied by large conformational changes upon peptidoglycan binding, whereby a loop regulates access to the active site. Furthermore, prior hydrolysis of the crosslinked peptide stem from the saccharide backbone of the peptidoglycan on one side is a prerequisite for its recognition and turnover by Pgp3. These analyses reveal the noncanonical nature of the transformations at the core of the events that define the morphological shape for C. jejuni as an intestinal pathogen.

Cloning of the bglX (PA1726) gene and purification of BglX wild-type and D286N variant S1 Generation of a bglX::Tn strain harboring a BglX-producing plasmid (bglX::Tn/pBglX) S1

Abstract:The effects of Electromagnetic radiations (EMR) are being felt by wildlife and the environment as a whole, birds, bees, worms, trees are being affected. So the main focus of present study was carried out to analyse the influence of cell phone radiations on the biochemical aspects of drone of Apis mellifera L. The drone was exposed for 30 mins to radiations using live cell phones kept in working mode with tape recorder at the speaker end and positive response at the receiver's end. The results of the treatment were analyzed and compared with the control. The concentration of various biomolecules increased from 1.65 mg/ml to 2.75 mg/ml for carbohydrates , 3.74 mg/ ml to 4.85 mg/ml for proteins and from 0.325 mg/ml to 1.33 mg/ml for lipids under the influence of EMR.

Lipozyme® TL IM mediated the selective deacetylation of one of the two acetoxy groups in 4-C-acetoxymethyl-5-O-acetyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-d-xylofuranose, leading to the first efficient syntheses of 3′-azido/3′-amino-xylobicyclonucleosides T, U, C and A.

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Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogues. AntiAspergillus activity was observed for an optically enriched derivative, (Ϫ)-S-2-(2=,4=-difluorophenyl)-1-hexyl-amino-3-(1ٞ,2ٞ,4ٞ)triazol-1ٞ-yl-propan-2-ol, which exhibits MIC values of 15.6 g/ml and 7.8 g/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 g/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against Aspergillus fumigatus (MIC, 1.63 g/ml).These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting antiAspergillus activity may have reduced toxicity. KEYWORDS chemoenzymatic synthesis, fluconazole, antifungal agents, AspergillusA spergillosis remains a significant threat to public health, and in spite of continuous efforts to improve timely diagnosis and clinical therapies, mortality caused by this disease remains unacceptably high (1, 2). Current therapeutic options for treating Aspergillus-induced disorders include antifungal agents such as polyenes, azoles, and echinocandins (3, 4). Thus, the discovery of new antifungal compounds remains important given the need to address the development of drug resistance in pathogenic fungi (5-7). One approach to accomplishing this goal is to prepare new derivatives of existing drugs with broad-spectrum activity and enhanced pharmacokinetic properties. As part of our ongoing efforts to use lipases (8-12), which catalyze reactions with high degrees of chemo-, regio-, and stereoselectivity in organic synthesis, we became interested in preparing new antifungals using biocatalysis.Fluconazole, introduced in 1990, is a bis-triazole antifungal drug which possesses

The aim of this investigation was to evaluate the antioxidant activity, mineral content and dietary fiber of unprocessed and processed pearl millet, sorghum and mung bean grains. The methanolic extracts of different grains flours were analyzed for 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. The samples were also evaluated for dietary fiber, mineral content and available mineral. The results indicated that the highest amount of total, soluble and insoluble dietary fibre content was present in mung bean. Maximum iron and zinc content was observed in unprocessed pearl millet whereas mung bean had highest amount of calcium content. Processing of grains improve the availability of minerals. Germinated mung bean showed DPPH free radical scavenging activity and total phenolic content.