On the mechanism and rate of spontaneous decomposition of amino acids.

Spontaneous decarboxylation of amino acids is among the slowest known reactions; it is much less facile than the cleavage of amide bonds in polypeptides. Establishment of the kinetics and mechanisms for this fundamental reaction is important for gauging the proficiency of enzymes. In the present study, multiple mechanisms for glycine decomposition in water are explored using QM/MM Monte Carlo simulations and free energy perturbation theory.

Effects of desipramine on the antioxidant status in rat tissues at carrageenan-induced paw inflammation.

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h.

Rigid substructure search.

Motivation: Identifying the location of binding sites on proteins is of fundamental importance for a wide range of applications, including molecular docking, de novo drug design, structure identification and comparison of functional sites. Here we present Erebus, a web server that searches the entire Protein Data Bank for a given substructure defined by a set of atoms of interest, such as the binding scaffolds for small molecules. The identified substructure contains atoms having the same names, belonging to same amino acids and separated by the same distances (within a given tolerance) as the atoms of the query structure.

Effect of plastoquinone derivative 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on contents of steroid hormones and NO level in rats.

Introduction of the plastoquinone derivative 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) into male Wistar rats once a day for two weeks in doses of 25 and 250 nmol/kg led to elevation of 17β-estradiol level in blood serum by 33 and 41%, respectively. At the same time, nitrate and nitrite contents in the rat blood serum increased by 49 and 34%, respectively. ESR spectroscopy with diethyldithiocarbamateiron complex as a spin trap showed more than twofold increase in NO production in lungs, but not in blood, liver, and intestines, following the SkQ1 daily introduction at a dose of 25 nmol/kg.

Effects of structural analogues of nociceptin(1-13)NH₂ on brain antioxidant status in kainic acid-treated rats.

The in vivo effects of nociceptin (N/OFQ(1-13)NH(2) ) and its structural analogues ([Dab(9) ]N/OFQ(1-13)NH(2) , [Dap(9) ]N/OFQ(1-13)NH(2) and [Cav(9) ]N/OFQ(1-13)NH(2) ) on the levels of lipid peroxidation and cell antioxidants (enzyme and non-enzyme) in brain of control and kainic acid (KA)-treated rats were studied. In control animals, [Dab(9) ]N/OFQ(1-13)NH(2) and [Dap(9) ]N/OFQ(1-13)NH(2) , unlike N/OFQ(1-13)NH(2) and [Cav(9) ]N/OFQ(1-13)NH(2) , slightly increased the brain lipid peroxidation; the rest of the parameters were unchanged by all neuropeptides tested. KA (0.

Lithium cluster anions: photoelectron spectroscopy and ab initio calculations.

Structural and energetic properties of small, deceptively simple anionic clusters of lithium, Li(n)(-), n = 3-7, were determined using a combination of anion photoelectron spectroscopy and ab initio calculations. The most stable isomers of each of these anions, the ones most likely to contribute to the photoelectron spectra, were found using the gradient embedded genetic algorithm program. Subsequently, state-of-the-art ab initio techniques, including time-dependent density functional theory, coupled cluster, and multireference configurational interactions methods, were employed to interpret the experimental spectra.

In vivo effects of pentoxifylline on enzyme and non-enzyme antioxidant levels in rat liver after carrageenan-induced paw inflammation.

The present study aimed to investigate the effects of pentoxifylline (PTX) on the carrageenan (CG)-induced paw oedema and on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver, 4 and 24 h after CG injection. PTX (50 mg kg(-1) , i.p.

H·(H2O)n clusters: microsolvation of the hydrogen atom via molecular ab initio gradient embedded genetic algorithm (GEGA).

A new version of the ab initio gradient embedded genetic algorithm (GEGA) program for finding the global minima on the potential energy surface (PES) of mixed clusters formed by molecules and atoms is reported. The performance of the algorithm is demonstrated on the neutral H·(H(2)O)(n) (n = 1-4) clusters, that is, a radical H atom solvated in 1-4 water molecules. These clusters are of a fundamental interest.

Promiscuous DNA alkyladenine glycosylase dramatically favors a bound lesion over undamaged adenine.

The human DNA alkyladenine glycosylase (AAG) is a DNA repair enzyme catalyzing the initial step of DNA repair via lesion excision. Its binding site has an incredible plasticity, and recognizes a variety of DNA lesions resulting from deamination or alkylation of adenine. Based on this plasticity, it is natural to wonder how, and if AAG can discriminate against undamaged adenine.

Photochemistry of DNA fragments via semiclassical nonadiabatic dynamics.

Forming upon absorption of a UV photon, excited states of DNA are subject to nonadiabatic evolution, via either internal conversion (IC) back to the ground state or mutagenesis. Nonadiabatic processes following the formation of the first singlet excited states, S1, in 10 different small DNA fragments--4 single 4'H-nucleosides, 2 Watson-Crick base pairs, and 4 nucleotide quartets--have been investigated. Simulations were done via the nonadiabatic direct trajectory surface hopping semiclassical dynamics.

Antimutagenic activity of mitochondria-targeted plastoquinone derivative.

The ability of cationic plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 +/- 0.

[Production of destruxins by coprotrophic Beauveria feline no. 7 strain].

Beauveria feline No. 7 strain was isolated from the shrewmouse wool and characterized by production of a complex of destruxins cyclodepsipeptides. The strain was shown to produce significant quatities of destruxin B and pseudodestruxin C.

Nucleophilic difluoromethylation and difluoromethylenation of aldehydes and ketones using diethyl difluoromethylphosphonate.

New methodology for difluoromethylation and difluoromethylenation of aldehydes and ketones based on nucleophilic fluorination using diethyl difluoromethylphosphonate (1) was developed.

Are nociceptin(1-13)NH2 and its structural analogue [ORN(9)]nociceptin(1-13)NH2 able to affect brain antioxidant status in control and kainic acid-treated rats?

In-vivo effects of nociceptin (N/OFQ(1-13)NH(2)) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzyme (glutathione) antioxidants in brain of control and kainic acid-treated rats were studied. N/OFQ(1-13)NH(2) effects were compared with those of its structural analogue [Orn(9)]N/OFQ(1-13)NH(2). Kainic acid (25 microg, i.

Origin of the activity drop with the E50D variant of catalytic antibody 34E4 for Kemp elimination.

In enzymes, multiple structural effects cooperatively lead to the high catalytic activity, while individually these effects can be small. The design of artificial enzymes requires the understanding and ability to manipulate such subtle effects. The 34E4 catalytic antibody, catalyzing Kemp elimination of 5-nitrobenzisoxazole, and its Glu50Asp (E50D) variant are the subject of the present investigation.

Catalytic mechanism and performance of computationally designed enzymes for Kemp elimination.

A series of enzymes for Kemp elimination of 5-nitrobenzisoxazole has been recently designed and tested. In conjunction with the design process, extensive computational analyses were carried out to evaluate the potential performance of four of the designs, as presented here. The enzyme-catalyzed reactions were modeled using mixed quantum and molecular mechanics (QM/MM) calculations in the context of Monte Carlo (MC) statistical mechanics simulations.

Effect of copper intoxication on rat liver proteasome activity: relationship with oxidative stress.

Copper toxicity is associated with formation of reactive oxygen species, which are capable to oxidize proteins. The selective removal of the latter by the 20S proteasome is considered an essential part of the cell antioxidant defense system. The aim of the present study was to investigate whether peptidase activities of rat liver proteasomes were affected by chronic (40 mg CuSO(4)/rat/daily with the drinking water for 2 weeks) and acute (20 mg/kg CuSO(4), s.

Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow.

Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs), and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow), and the lamellum (zone of slow flow located between the lamellipodium and the cell body). Cell migration involves expansion of both the lamellipodium and the lamellum, as well as formation of new FAs, but it is largely unknown how the position of the boundary between the two flow zones is defined, and how FAs and actin flow mutually influence each other. We investigated dynamic relationship between focal adhesions and the boundary between the two flow zones in spreading cells.

First Report of Anthracnose of Salsola tragus Caused by Colletotrichum gloeosporioides in Russia.

In October of 2006, dying Salsola tragus L. (Russian thistle, tumbleweed), family Chenopodiaceae, plants were found along the Azov Sea at Chushka, Russia. Approximately 40 plants in the area were diseased and almost 80% of these were dying.

Evolution of cell interactions with extracellular matrix during carcinogenesis.

Interaction of cells with extracellular matrix (ECM) largely defines migration capacity of cells and ways of their dissemination in normal tissue processes and during tumor progression. We review current knowledge about structure of cell adhesions with ECM and their alterations during carcinogenesis. We analyze how changes in structure of cell-matrix adhesions and ECM itself lead to acquisition of neoplastic properties by cells.

Regulation of polarity in cells devoid of actin bundle system after treatment with inhibitors of myosin II activity.

Interplay of two cytoskeletal systems--microfilaments and microtubules is essential for directional cell movement. To better understand the role of those cytoskeletal systems in polarization of cells, rat fibroblasts were incubated with drugs inhibiting activity of myosin II: blebbistatin and Y-27632. Both drugs led to disappearance of actin-myosin bundles and mature focal cell-matrix adhesions but did not affect polarization and directional motility.

In vitro effects of alloxan/copper combinations on lipid peroxidation, protein oxidation and antioxidant enzymes.

The in vitro effects of alloxan and the product of its reduction dialuric acid (alone or in combination with copper ions) on lipid peroxidation, carbonyl content, GSH level and antioxidant enzyme activities in rat liver and kidney have been studied. The effects of Cu2+/alloxan and Cu2+/dialuric acid were compared with those of Fe3+/alloxan and Fe3+/dialuric acid. Unlike alloxan, dialuric acid increased liver and kidney lipid peroxidation; similar effects were registered in the presence of Fe3+.

Effects of proteasome inhibitor, MG132, on proteasome activity and oxidative status of rat liver.

In vivo effects of N-benzyloxycarbonyl (Cbz)-Leu-Leu-leucinal (MG132) on chymotryptic-like (ChT-L), tryptic-like, and post-glutamyl peptide hydrolytic-like proteasome activities, protein oxidation, lipid peroxidation (LP), glutathione (GSH) level, as well as on the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-reductase) in the rat liver were studied. The possibility of MG132 provoking the formation of free oxygen radicals was also assayed in primary hepatocytes. The following results were obtained: (1) In vivo, MG132 did not change the spontaneous LP, but increased Fe-induced LP and the amount of oxidized proteins; it decreased the GSH level in liver.

Polarization Effects for Hydrogen-Bonded Complexes of Substituted Phenols with Water and Chloride Ion.

Variations in hydrogen-bond strengths are investigated for complexes of nine para-substituted phenols (XPhOH) with a water molecule and chloride ion. Results from ab initio HF/6-311+G(d, p) and MP2/6-311+G(d, p)//HF/6-311+G(d, p) calculations are compared with those from the OPLS-AA and OPLS/CM1A force fields. In the OPLS-AA model, the partial charges on the hydroxyl group of phenol are not affected by the choice of para substituent, while the use of CM1A charges in the OPLS/CM1A approach does provide charge redistribution.

Effect of MG132 on proteasome activity and prooxidant/antioxidant status of rat liver subjected to ischemia/reperfusion injury.

Aim: Previous studies have shown that proteasome inhibitors exerted protective effects against ischemia/reperfusion injury (IRI) of brain, heart, kidney and intestine. The aim of the present study was to investigate: (i) whether the proteasome inhibitor MG132 protects rat liver against IRI; and (ii) whether MG132 modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.

Methods: The left lateral and medial lobes (approximately 70% of the total liver volume) of livers of male Wistar rats were subjected to 30-min ischemia followed by 60-min reperfusion.