Calcium and copper transport ATPases: analogies and diversities in transduction and signaling mechanisms

The calcium transport ATPase and the copper transport ATPase are members of the P-ATPase family and retain an analogous catalytic mechanism for ATP utilization, including intermediate phosphoryl transfer to a conserved aspartyl residue, vectorial displacement of bound cation, and final hydrolytic cleavage of Pi. Both ATPases undergo protein conformational changes concomitant with catalytic events. Yet, the two ATPases are prototypes of different features with regard to transduction and signaling mechanisms. The calcium ATPase resides stably on membranes delimiting cellular compartments, acquires free Ca2+ with high affinity on one side of the membrane, and releases the bound Ca2+ on the other side of the membrane to yield a high free Ca2+ gradient. These features are a basic requirement for cellular Ca2+ signaling mechanisms. On the other hand, the copper ATPase acquires copper through exchange with donor proteins, and undergoes intracellular trafficking to deliver copper to acceptor proteins. In addition to the cation transport site and the conserved aspartate undergoing catalytic phosphorylation, the copper ATPase has copper binding regulatory sites on a unique N-terminal protein extension, and has also serine residues undergoing kinase assisted phosphorylation. These additional features are involved in the mechanism of copper ATPase intracellular trafficking which is required to deliver copper to plasma membranes for extrusion, and to the trans-Golgi network for incorporation into metalloproteins. Isoform specific glyocosylation contributes to stabilization of ATP7A copper ATPase in plasma membranes

Catalytic epoxidation and sulfoxidation activity of a dioxomolybdenum(VI) complex bearing a chiral tetradentate oxazoline ligand

A dioxomolybdenum(VI) complex bearing a tetradentate anionic N,O oxazoline ligand with four stereocenters has been studied as a catalyst in the liquid-phase epoxidation of 17 different aliphatic and aromatic olefins(including prochiral, racemate or pure enantiomers) using tert-butyl hydroperoxide as the oxidant. Epoxide selectivities of up to 100% and variable epoxide yields (3–100% within 24 h) were obtained. Although the complex generally exhibited low or no chiral induction ability, diastereoselectivity was significant in some cases (in the reaction of limonene, for example). Kinetic studies and recycling tests with the substrates cis-cyclooctene and trans-b-methylstyrene showed that the catalyst is stable and reusable, and recycling is facilitated by immobilization of the complex in a room temperature ionic liquid. Preliminary results show that the complex may have a broad substrate scope, not only for olefin epoxidation, but also for the dehydrogenation of alcohols to carbonyl compounds and the sulfoxidation of sulfides to sulfoxides

Pregabalin antagonizes copper-induced toxicity in the brain: in vitro and in vivo studies.

Copper plays key roles in brain metabolism. Disorders of copper metabolism impact on neural signaling. The intracellular and extracellular concentrations of copper are tightly regulated. Pregabalin is a drug with multiple modes of action and has a high-affinity binding site for the alpha2delta subunit of voltage-gated calcium channels.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

First principles and integrated modelling achievements towards trustful fusion power predictions for JET and ITER

Predictability of burning plasmas is a key issue for designing and building credible future fusion devices. In this context, an important effort of physics understanding and guidance is being carried out in parallel to JET experimental campaigns in H and D by performing analyses and modelling towards an improvement of the understanding of DT physics for the optimization of the JET-DT neutron yield and fusion born alpha particle physics. Extrapolations to JET-DT from recent experiments using the maximum power available have been performed including some of the most sophisticated codes and a broad selection of models. There is a general agreement that 11-15 MW of fusion power can be expected in DT for the hybrid and baseline scenarios. On the other hand, in high beta, torque and fast ion fraction conditions, isotope effects could be favourable leading to higher fusion yield. It is shown that alpha particles related physics, such as TAE destabilization or fusion power electron heating, could be studied in ITER relevant JET-DT plasmas