Potentiometric and calorimetric study on stability of nicotinamide complexes of silver(I) and copper(II) in aqueous ethanol and dimethylsulfoxide

The complex formation between silver(I) and nicotinamide as well as between copper(II) and nicotinamide in water-ethanol and water-dimethylsulfoxide media was studied by means of potentiometric technique. The heat of complex formation was measured using the method of precision calorimetry. The experimental data have been considered from the point of view of thermodynamic characteristics of the reagents and their solvation.     

The structure of pepsin. II. Structure of the enzyme active site (at 2 angstroms resolution)

Detailed structure of the pepsin active site in the region of the active aspartic acid residues and substrate binding S1 and S1' sites is considered. At the active site of the enzyme crystals studied several molecules of ethanol were detected, which interact with active groups. The catalytic properties of aspartyl proteinases towards dipeptide substrates were explained on the base of the specific structure of S1 and S1' binding sites.     

Experimental infection of ixodid ticks with Karshi virus

The ixodid ticks Hyalomma asiaticum, H. anatolicum, Dermacentor niveus were infected experimentally with Karsha virus. The virus replication has been proved to occur in the tick's organism. The titre of the virus grows gradually in infected ticks. Entering the tick's gut during its feeding virus particles penetrate into the gut walls where primary multiplication and accumulation of the virus take place.     

Hemorheological Status of a Body with a Normal vs. Changed Vascular Bed

The results of a comprehensive study of blood rheology in subjects with a normal or changed vascular bed show that chronic venous and arterial insufficiency in the lower limbs, caused by morphological changes in vessels, is accompanied by a decrease in the blood fluidity. This impairs the efficiency of oxygen supply to tissues. The authors detected rheological shifts that facilitate increases in the blood viscosity.     

Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model

Inflammation and oxidative stress play fundamental roles in the pathogenesis of atherosclerosis. Myeloperoxidase has been extensively implicated as a key mediator of inflammatory and redox-dependent processes in atherosclerosis. However, the effect of synthetic myeloperoxidase inhibitors on atherosclerosis has been insufficiently studied. In this study, ApoE^−/− mice were randomized to low- and high-dose INV-315 groups for 16 weeks on high-fat diet. INV-315 resulted in reduced plaque burden and improved endothelial function in response to acetylcholine. These effects occurred without adverse events or changes in body weight or blood pressure. INV-315 treatment resulted in a decrease in iNOS gene expression, superoxide production and nitrotyrosine content in the aorta. Circulating IL-6 and inflammatory CD11b⁺/Ly6G^low/7/4^hi monocytes were significantly decreased in response to INV-315 treatment. Acute pretreatment with INV-315 blocked TNFα-mediated leukocyte adhesion in cremasteric venules and inhibited myeloperoxidase activity. Cholesterol efflux was significantly increased by high-dose INV-315 via ex-vivo reverse cholesterol transport assays. Our results suggest that myeloperoxidase inhibition may exert anti-atherosclerotic effects via inhibition of oxidative stress and enhancement of cholesterol efflux. These findings demonstrate a role for pharmacologic modulation of myeloperoxidase in atherosclerosis.     

2,5-Diketopiperazines: A New Class of Poly(ADP-ribose)polymerase Inhibitors

We show for the first time that natural 2,5-diketopiperazines (cyclic dipeptides) can suppress the activity of the important anticancer target poly(ADP-ribose)polymerase (PARP). Cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) can interact with the key residues of the PARP-1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) forms hydrogen bonds with the Gly863 residue, while the second amide group can form a hydrogen bond with the catalytic residue Glu988, and the side chain can make a hydrophobic contact with Ala898. Newly identified diketopiperazine inhibitors are promising basic structures for the design of more effective inhibitors of PARP family enzymes. The piperazine core with two chiral centers provides many opportunities for structural optimization.     

Various aspects of structural studies of aspartate proteinases

The paper is a brief account of aspartic proteinases' structural studies developed in V.A. Engelhardt Institute of Molecular Biology during the last 3 years. The work on porcine pepsin has been finalized after the refinement of the monoclinic crystal form at 1.8 A resolution performed in collaboration with the group of protein structure and function studies of the University of Alberta in Canada. An important structural property of chymosin which explains the enzyme specificity has been found. Protein engineering work on chymosin is being developed. The structural template for aspartic proteinases has been elucidated and on the basis of this template the model of HIV-1 protease molecule has been built. Some approaches to the design of HIV-1 protease inhibitors were elucidated.     

Genetic and phenotypic differences between thistle populations in response to habitat and weed management practices

Rapid evolutionary change is increasingly being recognized as commonplace, but the evolutionary consequences for species and ecosystems under human‐induced selection regimes have not been explored in detail, although many species occur in such environments. In a common garden experiment and with amplified fragment length polymorphism markers, we examined whether genetic differentiation has taken place between spatially intermixed populations of creeping thistles Cirsium arvense (Asteraceae) collected from a natural habitat (maritime shores), a semi‐natural habitat (road verges) and arable fields under two management regimes: conventional and organic farming. Populations of C. arvense have altered genetically and locally adapted their growth patterns with changed land use. Although plants from different habitats showed similar total biomass production, shoot and root production was higher for maritime populations, suggesting selection for increased competitive ability. Competitive ability then declined in the order semi‐natural, conventional farms and organic farms. Thistles in arable fields may be more selected for tolerance against disturbances from herbicides and mechanical weed control. In addition, early shoot sprouting and genetic analysis showed differentiation between plants originating from conventional farms and farms that were converted to organic 9–30 years ago, suggesting some adaptation to altered crop cultivation practices. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 99 , 797–807.     

Design and structural thermodynamic studies of the chimeric protein derived from spectrin SH3 domain

A number of the chimeric constructs with spectrin SH3 domain were designed for structural and thermodynamic studies of protein self-assembly and protein-ligand interactions. SH3 domains, components of many regulatory proteins, operate through weak interactions with proline-rich regions of polypeptide chains. The recombinant construct (WT-CIIA) studied in this work was constructed by linking the peptide ligand PPPVPPYSAG to the domain C-terminus via a long 12-residue linker to increase the affinity of this ligand for the spectrin domain, thereby ensuring a stable positioning of the polyproline helix to the conserved ligand-binding site in orientation II, which is regarded as untypical of the interaction between this domain and oligopeptides. A comparison of fluorescence spectra of the initial domain and the recombinant protein WT-CIIA suggests that the ligand sticks to the conservative binding site. However, analysis of the equilibrium urea-induced unfolding has demonstrated that this is an unstable contact, which leads to a two-stage unfolding of the chimeric protein. The protein WT-CIIA was crystallized; a set of X-ray diffraction data with a resolution of 1.75 Å was recorded from individual crystals. A preliminary analysis of these diffraction data has demonstrated that the crystals belong to space group P32 with the following unit cell parameters: a = b = 36.39, c = 112.17 Å, a = β = 90.0, and γ = 120.0.