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The DNA-dependent protein kinase (DNA-PK) is a trimeric nuclear serine/threonine protein kinase consisting of a large catalytic sub-unit and the Ku heterodimer that regulates kinase activity by its association with DNA. DNA-PK is a major component of the DNA double strand break repair apparatus, and cells deficient in one of its component are hypersensitive to ionizing radiation. DNA-PK is also required...
Eukaryotic cells respond to radiation-induced damage in DNA and other cellular components by turning on cascades of regulatory events which constitute a complex network of pathways of cell cycle checkpoints, DNA repair and damage tolerance mechanisms, recombination and delayed cell death (apoptosis). By virtue of the high homology in structure and function of yeast and mammalian proteins several DNA...
Lipases from Pseudomonas bacteria are widely used for a variety of biotechnological applications. Overexpression in heterologous hosts like Escherichia coli failed to produce enzymatically active lipase prompting to study the molecular mechanisms underlying the regulation of lipase gene expression and secretion. The prototype lipase from P. aeruginosa is encoded in a bicistronic operon which is transcribed...
Escherichia coli strains VIP596 and VIP597 have been constructed to compare the amount of transcription of the ftsZ gene derived from proximal promoters in the ddlB-ftsZ region with that originating in the upstream regions of the dcw cluster. Both strains have in common a β-galactosidase reporter fusion located at the ddlB locus, but differ in that VIP597 has a transcription terminator Ω interposon...
The 11 kb las locus, present on the 50 kb plasmid pCIM1, specifies the production of the lantibiotic lactocin S in Lactobacillus sakei L45. The gene cluster is organized into two oppositely orientated operons, lasAMNTUVPJW (lasA-W) and lasXY, the former of which contains the biosynthetic, immunity and transport genes. We have previously shown that inactivation of lasX abolishes lactocin S production...
Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected...
Phosphatidic acid phosphohydrolase-1 (PAP-1) activity is reversibly inhibited by fatty acids and their acyl-CoA esters and it appears paradoxical that these effectors have been reported to increase the liver’s esterification capacity by translocating the rate-limiting enzyme PAP-1 from cytosol to the endoplasmic reticulum. Therefore, we have examined the effect of oleate, oleoyl-CoA, and spermine...
An important challenge in environmental biogeochemistry is the determination of the bioavailability of toxic and essential trace compounds in natural media. For trace metals, it is now clear that chemical speciation must be taken into account when predicting bioavailability. Over the past 20 years, equilibrium models (free ion activity model (FIAM), biotic ligand model (BLM)) have been increasingly...
Glycolytic enzymes reversibly associate with the human erythrocyte membrane (EM) as part of their regulatory mechanism. The site for this association has been described as the amino terminus of band 3, a transmembrane anion transporter. Binding of glycolytic enzymes to this site is recognized to inhibit glycolysis, since binding inhibits the catalytic activity of these enzymes, including the rate-limiting...
In metazoan organisms protein inhibitors of peptidases are important factors essential for regulation of proteolytic activity. In vertebrates genes encoding peptidase inhibitors constitute up to 1% of genes reflecting a need for tight and specific control of proteolysis especially in extracellular body fluids. In stark contrast unicellular organisms, both prokaryotic and eukaryotic consistently contain...
Post-genomic data show unexpected extent of the transcribed genome and the size of individual primary transcripts. Hence, most cis-regulatory modules (CRMs) binding transcription factors (TFs) at promotor, enhancer and other sites are actually transcribed within full domain transcripts (FDTs). The ensemble of these CRMs placed way upstream of exon clusters, downstream and in intronic or intergenic...
Addition of the plant hormone 24-epibrassinolide to culture media stimulated the growth of a freshwater diatom, Asterionella formosa. The hormone stimulated activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme from Calvin cycle, by 6-fold. Other key metabolic enzymes, phosphofructokinase and malate dehydrogenase were also stimulated but to a lesser extent. The activity of glucose-6-phosphate...
The cholesterol biosynthesis pathway has recently been shown to play an important role in the innate immune response to viral infection with host protection occurring through a coordinate down regulation of the enzymes catalysing each metabolic step. In contrast, statin based drugs, which form the principle pharmaceutical agents for decreasing the activity of this pathway, target a single enzyme....
In the plastids of plant cells, fatty acid (FA) production is a central biosynthetic process. It provides acyl chains for the formation of a variety of acyl lipids fulfilling different biological functions ranging from membrane synthesis to signaling or carbon and energy storage. The biochemical pathway leading to the synthesis of FA has been described for a long time. Over the last 15 years, and...
Prothrombin is activated to thrombin by the prothrombinase complex through sequential cleavage at two distinct sites. This occurs at sites of vascular injury in a highly regulated cascade of serine protease and cofactor activation, where activated platelets provide a suitable surface for protease/cofactor/substrate assembly. The precise structural and conformational changes undergone during the transition...
The enterobacterial pathogen Salmonella has long served as a model for bacterial pathogenesis, stress response, gene expression and regulation with extensive investigation involving protein function. With the advent of high-throughput sequencing technologies and their applications in genomics and transcriptomics, a wealth of data particularly with respect to small RNAs (sRNAs) is being generated....
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