Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)

Background  

The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin.     

Comparative molecular field analysis and molecular dynamics studies of α/β hydrolase domain containing 6 (ABHD6) inhibitors

The endocannabinoid system remains an attractive molecular target for pharmacological intervention due to its roles in the central nervous system in learning, thinking, emotional function, regulation of food intake or pain sensation, as well as in the peripheral nervous system, where it modulates the action of cardiovascular, immune, metabolic or reproductive function. α/β hydrolase domain containing 6 (ABHD6)—an enzyme forming part of the endocannabinoid system—is a newly discovered post-genomic protein acting as a 2-AG (2-arachidonoylglycerol) serine hydrolase. We have recently reported a series of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors. Here, we present comparative molecular field analysis (CoMFA) and molecular dynamics studies of these compounds. First, we performed a homology modeling study of ABHD6 based on the assumption that the catalytic triad of ABHD6 comprises Ser148–His306–Asp 278 and the oxyanion hole is formed by Met149 and Phe80. A total of 42 compounds was docked to the homology model using the Glide module from the Schrödinger suite of software and the selected docking poses were used for CoMFA alignment. A model with the following statistics was obtained: R ² = 0.98, Q ² = 0.55. In order to study the molecular interactions of the inhibitors with ABHD6 in detail, molecular dynamics was performed with the Desmond program. It was found that, during the simulations, the hydrogen bond between the inhibitor carbonyl group and the main chain of Phe80 is weakened, whereas a new hydrogen bond with the side chain of Ser148 is formed, facilitating the possible formation of a covalent bond.

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Graphical Abstract Left–right: Docking pose of 1 in the binding pocket of α/β hydrolase domain containing 6 (ABHD6) selected for molecular alignment; CoMFA steric and electrostatic contour fields; changes in potential energy of the complex during simulations for the complex of 6 and ABHD6

     

Polyamines may regulate S-phase progression but not the dynamic changes of chromatin during the cell cycle

Several studies suggest that polyamines may stabilize chromatin and play a role in its structural alterations. In line with this idea, we found here by chromatin precipitation and micrococcal nuclease (MNase) digestion analyses, that spermidine and spermine stabilize or condense the nucleosomal organization of chromatin in vitro. We then investigated the possible physiological role of polyamines in the nucleosomal organization of chromatin during the cell cycle in Chinese hamster ovary (CHO) cells deficient in ornithine decarboxylase (ODC) activity. An extended polyamine deprivation (for 4 days) was found to arrest 70% of the odc⁻ cells in S phase. MNase digestion analyses revealed that these cells have a highly loosened and destabilized nucleosomal organization. However, no marked difference in the chromatin structure was detected between the control and polyamine-depleted cells following the synchronization of the cells at the S-phase. We also show in synchronized cells that polyamine deprivation retards the traverse of the cells through the S phase already in the first cell cycle. Depletion of polyamines had no significant effect on the nucleosomal organization of chromatin in G₁–early S. The polyamine-deprived cells were also capable of condensing the nucleosomal organization of chromatin in the S/G₂ phase of the cell cycle. These data indicate that polyamines do not regulate the chromatin condensation state during the cell cycle, although they might have some stabilizing effect on the chromatin structure. Polyamines may, however, play an important role in the control of S-phase progression. J. Cell Biochem. 68:200–212, 1998. © 1998 Wiley-Liss, Inc.     

Lipids and apolipoproteins A-I, B and C-II and different rapid weight loss programs (weight lifters, wrestlers, boxers and judokas)

Apolipoproteins A-I, B, C-II and lipids were studied before and after rapid weight loss schedules. The compared groups were all athletic. Apolipoproteins were determined by electroimmunoassay methods using apoproteins purified by chromatofocusing column method. Dextran T10 was shown to increase rocket height in ApoB assay. Over 1% Dextran concentrations gave poor response. The linearity during calibration was from 0.3 to 3.0 g ApoB/l. Baseline values of ApoA-I in wrestlers, weightlifters, boxers and judokas were slightly higher as compared to "normal" population; ApoB was clearly reduced (mean value of 690 mg/l). Weight-loss was significant in each experimental group; mean value of 4.1% in active exercise, sauna and diuretic groups together. Compared as the whole sportsmen group in passive weight loss (or sauna) and diuretic groups the most pronounced changes were seen to be elevated apoprotein concentrations, whereas weight-loss by active rapid exercise resulted no apoprotein changes, but instead an increment in HDL cholesterol and decrement in triglycerides, respectively. The present study was the first to evaluate baseline values of apoproteins A-I, B and C-II in first class athletes and also the possible changes in these and lipid values in rapid weight-loss practices.     

Acid stress in respect to calcium and magnesium concentrations in the plasma of perch during maturation and spawning

Synopsis Plasma calcium and magnesium concentrations in perch,Perca fluviatilis, were monitored in an acid lake, Lake Iso Tenhetty (pH ∼5, Al concentrations 0.3–0.5 mg l^-1) compared with a nearby reference lake, Lake P?ij?nne, in Southern Finland. The effect of acid stress could be noticed as 1/3 lower fecundity of perch in the acid lake. Plasma Ca concentrations were temporarily lower in the middle of the winter in the fish of the acid lake, and in April–May samples the situation was opposite. Plasma Mg concentration was also lower in the perch from the acid lake in midwinter months, when compared with the double as high values (∼3 mmol l^-1) from the reference lake. Elevated level of plasma Mg have been reported for fish in cold acclimation especially in winter. Thus overwintering may be specially stressing for some specimens in acid waters. Also ova did contain clearly less magnesium in the midwinter sample from the acid lake perch compared with the reference lake sample. This difference, however, was no more to be found later in spring. Mg content in the ova of perch was in both cases high, which may be necessary to the breeding in comparable acid waters. According to the literature fish cannot increase their magnesium content directly from the water. Mortality for the reference lake embryos was lower than those of the acid lake when incubated in the acid lake. No physiological acclimation inside the fish could be demonstrated in this case.