Dynamic allostery: linkers are not merely flexible

Most proteins consist of multiple domains. How do linkers efficiently transfer information between sites that are on different domains to activate the protein? Mere flexibility only implies that the conformations would be sampled. For fast timescales between triggering events and cellular response, which often involves large conformational change, flexibility on its own may not constitute a good solution. We posit that successive conformational states along major allosteric propagation pathways are pre-encoded in linker sequences where each state is encoded by the previous one. The barriers between these states that are hierarchically populated are lower, achieving faster timescales even for large conformational changes. We further propose that evolution has optimized the linker sequences and lengths for efficiency, which explains why mutations in linkers may affect protein function and review the literature in this light.     

Characterization and anions inhibition studies of an α-carbonic anhydrase from the teleost fish Dicentrarchus labrax

Carbonic anhydrase (CA; EC 4.2.1.1) was purified from the gill of the teleost fish Dicentrarchus labrax (European seabass). The purification procedure consisted of a single step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The enzyme was purified 84.9-fold with a yield of 58%, and a specific activity of 838.9 U/mg proteins. It has an optimum pH at 8.0; an optimum temperature at 10°C. The kinetic parameters of this enzyme were determined for its esterase activity, with 4-nitrophenyl acetate (NPA) as substrate. The following anions, H?NSO??, I?, SCN?, NO??, NO??, N??, Br?, Cl?, SO?2?, and F? showed inhibitory effects on the enzyme. Sulfamic acid, iodide, and thiocyanate exhibited the strongest inhibitory action, in the micromolar range (K(i)s of 87-187 μM). NO??, NO?? and N?? were moderate inhibitors, whereas other anions showed only weak actions. All tested anions inhibited the enzyme in a competitive manner. Our findings indicate that these anions inhibit the fish enzyme in a similar manner to other α-CAs from mammals investigated earlier, but the susceptibility to various anions differs significantly between the fish and mammalian CAs.     

Psephellus yusufeliensis sp. nov. from north-east Anatolia, Turkey

Psephellus yusufeliensis O. Tugay & Uysal sp. nov. (Asteraceae) from Yusufeli (B7 Artvin-Turkey) is described and illustrated. It is closely related to P. aucheriana (DC) Wagenitz & F. H. Hellw. Diagnostic morphological characters are provided and the relationship to other Psephellus species in Turkey is discussed. The geographical distribution of the new species and other related species are mapped. Notes are also presented on the ecology, biogeography and conservation status of the new species.     

Genotoxicity of five food preservatives tested on root tips of Allium cepa L

The effects of the food preservatives sodium benzoate (SB), boric acid (BA), citric acid (CA), potassium citrate (PC) and sodium citrate (SC) have been studied on root tips of Allium cepa L. Roots of A. cepa were treated with a series of concentrations, ranging from 20 to 100 ppm for 5, 10 and 20 h. The results indicate that these food preservatives reduced mitotic division in A. cepa compared with the respective control. Mitotic index values were generally decreased with increasing concentrations and longer treatment times. Additionally, variations in the percentage of mitotic stages were observed. The total percentage of aberrations generally increased with increasing concentrations of these chemicals and the longer period of treatment. Different abnormal mitotic figures were observed in all mitotic phases. Among these abnormalities were anaphase bridges, C-mitosis, micronuclei, lagging, stickiness, breaks and unequal distribution.     

Pretreatment Effect of Resveratrol on Streptozotocin-Induced Diabetes in Rats

This study was planned to investigate the pretreatment effect of resveratrol on streptozotocin-induced diabetic rats. The control group consisted of 10 male albino Sprague–Dawley rats, 10–12 weeks of age, weighing approximately 295 g. The first experimental group consisted of 15 albino Sprague–Dawley rats, 10–12 weeks of age, weighing approximately 305 g. This group was administered streptozotocin (55 mg/kg, intraperitoneally). The second experimental group (n = 15) was administered resveratrol (0.5 ml/day) 10 days before streptozotocin induction. A training period was performed for all groups before the experimental procedure, and systolic arterial blood pressures and heart rates were recorded daily. At the end of the 10th day, blood samples of control and experimental groups were drawn. Total nitrite, nitrite, nitrate, malondialdehyde (MDA), copper, and zinc concentrations in plasma were measured both in control and experimental groups. Additionally, superoxide dismutase, catalase activities, and copper and zinc concentrations in red cell were determined in each group. At the end of the study, increases in catalase activity, nitric oxide level, and zinc concentrations and decreases in lipid peroxidation product MDA and copper concentrations were found in the resveratrol-pretreated diabetic group when compared to the diabetic group. This study was presented at “The 5th International Congress of Pathophysiology (ISP2006)” June 28–July 1, 2006, Beijing, China.     

Investigation of the effects of α-tocopherol on the levels of Fe,Cu, Zn,Mn, and carbonic anhydrase in rats with bleomycin-induced pulmonary fibrosis

This study was designed to examine the effects of vitamin E on the levels of Zn, Mn, Cu, Fe, and carbonic anhydrase in rats with bleomycin-induced pulmonary fibrosis. Twenty-one male Wistar albino rats were randomly divided into three groups: bleomycin alone, bleomycin+vitamin E, and saline alone (control group). The bleomycin group was given 7.5 mg/kg body weight (single dose) bleomycin hydrochloride intratracheally. The bleomycin+vitamin E group was also instilled with bleomycin hydrochloride but received injections of α-tocopherol twice a week. The control group was treated with saline alone. Animals were sacrified 14 d after intratracheal instillation of bleomycin. Tissue Zn, Mn, Cu, Fe, and carbonic anhydrase activities were measured in the lung and liver. Lung Cu, Fe, and carbonic anhydrase activity increase in both experimental groups. Zn and Mn levels decreased, except for the Mn level in the bleomycin group. Liver Zn, Mn, and Cu levels decreased in both experimental groups compared to the control group, whereas Fe and carbonic anhydrase activity increased in comparison to the control group. However, the liver tissue Fe level decreased compared to the control group. In the histopathologic assesment of lung sections in the bleomycin+vitamin E group, partial fibrotic lesions were observed, but the histopathologic changes were much less severe compared to the bleomycin-treated group.     

A discriminative method for remote homology detection based on n-peptide compositions with reduced amino acid alphabets

In this study, n-peptide compositions are utilized for protein vectorization over a discriminative remote homology detection framework based on support vector machines (SVMs). The size of amino acid alphabet is gradually reduced for increasing values of n to make the method to conform with the memory resources in conventional workstations. A hash structure is implemented for accelerated search of n-peptides. The method is tested to see its ability to classify proteins into families on a subset of SCOP family database and compared against many of the existing homology detection methods including the most popular generative methods; SAM-98 and PSI-BLAST and the recent SVM methods; SVM-Fisher, SVM-BLAST and SVM-Pairwise. The results have demonstrated that the new method significantly outperforms SVM-Fisher, SVM-BLAST, SAM-98 and PSI-BLAST, while achieving a comparable accuracy with SVM-Pairwise. In terms of efficiency, it performs much better than SVM-Pairwise. It is shown that the information of n-peptide compositions with reduced amino acid alphabets provides an accurate and efficient means of protein vectorization for SVM-based sequence classification.