The structure of a shellfish specific GST class glutathione S‐transferase from antarctic bivalve Laternula elliptica reveals novel active site architecture

Glutathione‐S‐transferases have been identified in all the living species examined so far, yet little is known about their function in marine organisms. In a previous report, the recently identified GST from Antarctic bivalve Laternula elliptica (LeGST) was classified into the rho class GST, but there are several unique features of LeGST that may justify reclassification, which could represent specific shellfish GSTs. Here, we determined the crystal structure of LeGST, which is a shellfish specific class of GST. The structural analysis showed that the relatively open and wide hydrophobic H‐site of the LeGST allows this GST to accommodate various substrates. These results suggest that the H‐site of LeGST may be the result of adaptation to their environments as sedentary organisms. Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Static and dynamic properties of mid-size liquid n- alkanes,C12∼C400: a molecular dynamics simulation study

ABSTRACT

In this paper, we have extended our previous study of the static and dynamic properties (self-diffusion coefficient D_self and friction coefficient ζ) of liquid n-alkane systems up C₄₀₀ at several temperatures (～2300?K) using molecular dynamics (MD) simulations in the canonical ensembles. For the small n-alkanes with n?≤?120 (n: the chain length), the chains are clearly ?R² _ee?/6?R² _g? ≥ 1 (1.06 ～ 1.44), which leads to the conclusion that the liquid n-alkanes are far away from the ideal chain regime. But for the n-alkanes of n?≥?160, the chains are ?R² _ee?/6?R² _g? ≈ 1, indicating that they are Gaussian. It is found that the long chains of these n-alkanes at high temperatures show abnormalities in density and friction coefficient. We observed a clear transition in the power law dependence of n-alkane self-diffusion coefficient on the molecular weight (M) of n-alkane, D_self ～ M^?γ, occurs in the range C₁₂₀～C₁₆₀ at temperatures of 318, and 618?K, corresponding to a crossover from the ‘oligomer’ to the ‘Rouse’ regime. The entanglement lengths (N_e) are calculated by the Z1 code and discussed shortly.     

Molecular dynamics simulation study for ion mobility of alkali earth metal cations in water at 25°C

We present the results of molecular dynamics simulations for alkali earth metal cations (Mg²⁺, Ca²⁺, Sr²⁺ and Ba²⁺) in an aqueous solution at 25°C using the extended simple point charge water potential with Ewald summation. The ion mobilities (defined by u_i = D_iz_iF/RT) obtained from the simulations are in good accord with the experimental measures. The strong divalent cation–water interactions explain well the static and dynamic properties of the alkali earth metal cations. The classical solvent-berg picture describes the ion mobilities of these cations in water adequately.     

Molecular dynamics simulations of carbon nanotube oscillators deformed by encapsulated copper nanowires

Pure carbon nanotube (CNT) oscillators are compared to the corresponding CNT oscillators encapsulating copper nanowires (Cu@CNTs) by molecular dynamics simulations. The classical oscillation theory provides a fairly good estimate of the mass dependence of the operating frequency when the CNT surface is not deformed by the Cu nanowire. The structural deformations of the CNT induced by the encapsulated copper nanowire have a greater effect on the oscillation frequency than the mass of the copper nanowire. The excess forces of the Cu@CNT oscillator are slightly higher than those of the CNT oscillator and the excess van der Waals forces induced by the inter-wall interactions are 17 times higher than the excess forces induced by the Cu nanowire–CNT interactions.     

Noise-Induced Inner Hair Cell Ribbon Loss Disturbs Central Arc Mobilization: A Novel Molecular Paradigm for Understanding Tinnitus

Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury.     

Cloning Vectors Based on Cryptic Plasmids Isolated from Lactic Acid Bacteria:Their Characteristics and Potential Applications in Biotechnology

Lactic acid bacteria (LAB) are Gram positive bacteria, widely distributed in nature, and industrially important as they are used in a variety of industrial food fermentations. The use of genetic engineering techniques is an effective means of enhancing the industrial applicability of LAB. However, when using genetic engineering technology, safety becomes an essential factor for the application of improved LAB to the food industry. Cloning and expression systems should be derived preferably from LAB cryptic plasmids that generally encode genes for which functions can be proposed, but no phenotypes can be observed. However, some plasmid-encoded functions have been discovered in cryptic plasmids originating from Lactobacillus, Streptococcus thermophilus, and Pediococcus spp. and can be used as selective marker systems in vector construction. This article presents information concerning LAB cryptic plasmids, and their structures, functions, and applications. A total of 134 cryptic plasmids collated are discussed.     

Molecular modeling study for conformational changes of Sirtuin 2 due to substrate and inhibitor binding

Sirtuin is a member of NAD⁺-dependent deacetylase family. The structural details of Sirtuin 2 (SIRT2) complex will be very useful to discover the drug which might have beneficial effects on various diseases like cancer, diabetes, etc. Unfortunately, SIRT2 complex structure is not available yet, hence molecular docking was carried out to dock the substrate (NAD⁺ and acetylated lysine) and inhibitor (sirtinol) in the NAD⁺ binding site. The suitable binding orientation of substrate and inhibitor in the SIRT2 active site was selected and subjected to 5?ns molecular dynamics simulations to adjust the binding orientation of inhibitor and substrate as well as to identify the conformational changes in the active site. The result provides an insight about 3D SIRT2 structural details as well as the importance of F96 in deacetylation function. In addition, our simulations revealed the displacement of F96 upon substrate and inhibitor binding, inducing an extended conformation of loop3 and changing its interactions with the rest of SIRT2. We believe that our study could be helpful to gain a structural insight of SIRT2 and to design the receptor-based inhibitors.     

Hybrid Oligomer of Cyclonucleotides and Deoxynucleotides. A High Anti Left-handed Double Helical DNA Structure

Abstract

It has been shown by us that oligonucleotides containing cyclonucleosides with a high anti glycosidic conformation take left-handed, single and double helical structures (S. Uesugi, J. Yano, E. Yano and M. Ikehara, J. Am. Chem. Soc. 99, 2313 (1977) and references therein). In order to see whether DNA can adopt the high anti left-handed double helical structure or not, a self-complementary hexanucleotide containing 6,2′-O-cyclocytidine (C^○), 8,2′-O-cyclo- guanosine (G^○), deoxycytidine and deoxyguanosine, C^○G^{○dCdGC ○}G^○, was synthesized. Corresponding hexanucleotide containing only cyclonucleosides, C^○G^○C^○G^○C^○G^○, was also synthesized. Their conformation was examined by UV, CD and ¹H NMR spectroscopy. C^○G^○C^○G^○C^○G^○ forms an unusually stable, left-handed duplex. Imino proton NMR spectra and the results of nuclear Overhauser effect experiments strongly suggest that C^○G^○dCdGC^○G^○ take a left-handed double helical structure where the deoxynucleoside residues are involved in hydrogen bonding and take a high anti glycosidic conformation. Thus it is revealed that DNA could form a high anti, left-handed double helix which is different from that of Z-DNA under some constrained conditions.     

Linear Dichroism Studies of Conformations of Carcinogen-DNA Adducts Application to Covalent Complexes Derived from the Reactions of the Two Enantiomers of 9,10-epoxy-9,10,11,12-Tetrahydrobenzo(e)pyrene with DNA

Abstract

The conformations of the adducts derived from the covalent binding of the two enantiomeric forms of 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene (BePE) with native DNA were investigated by the electric linear dichroism technique. Both enantiomers give rise to two major adducts, one of which appears to be a quasi-intercalative site (I) while the other one is an external binding site (II). While the overall linear dichroism spectra are similar, in the case of the (—) enantiomer there is a greater contribution of site II adducts. These results are markedly different from the ones obtained with the two enantiomers of anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), where the (+) enantiomer gives rise almost exclusively to site II binding, while the (—) enantiomer gives rise to both site I and site II covalent binding. The differences in the heterogeneity of binding between BePE and anti-BaPDE enantiomers may be due to the absence of hydroxyl groups in BePE which, in the case of BaPDE, are an important factor in determining the stereoselective properties of the covalent binding to double-stranded DNA.