A selective class of inhibitors for the CLC-Ka chloride ion channel.

CLC proteins are a ubiquitously expressed family of chloride-selective ion channels and transporters. A dearth of pharmacological tools for modulating CLC gating and ion conduction limits investigations aimed at understanding CLC structure/function and physiology. Herein, we describe the design, synthesis, and evaluation of a collection of -arylated benzimidazole derivatives (BIMs), one of which (BIM1) shows unparalleled (>20-fold) selectivity for CLC-Ka over CLC-Kb, the two most closely related human CLC homologs.

Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in flavonoid biosynthetic pathway.

Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1.

Competing for ideal bodies: a study of exergames used as teaching aids in schools.

Since the development of the welfare state, the Swedish school subject Health and Physical Education (HPE) has been regarded as an important site for public health work, and still assumes a central role in promoting the health of the coming generation. A specific type of health intervention, promoted by researchers in recent years, is the use of so-called exergames. In some countries, these fitness games are used as teaching aids in physical education classes and can be seen as examples of how public health issues and popular culture are shaping HPE in schools.

The Escherichia coli CysZ is a pH dependent sulfate transporter that can be inhibited by sulfite.

The Escherichia coli inner membrane protein CysZ mediates the sulfate uptake subsequently utilized for the synthesis of sulfur-containing compounds in cells. Here we report the purification and functional characterization of CysZ. Using Isothermal Titration Calorimetry, we have observed interactions between CysZ and its putative substrate sulfate.

A designed inhibitor of a CLC antiporter blocks function through a unique binding mode.

The lack of small-molecule inhibitors for anion-selective transporters and channels has impeded our understanding of the complex mechanisms that underlie ion passage. The ubiquitous CLC "Chloride Channel" family represents a unique target for biophysical and biochemical studies because its distinctive protein fold supports both passive chloride channels and secondary-active chloride-proton transporters. Here, we describe the synthesis and characterization of a specific small-molecule inhibitor directed against a CLC antiporter (ClC-ec1).

Crystal structures of cobalamin-independent methionine synthase (MetE) from Streptococcus mutans: a dynamic zinc-inversion model.

Cobalamin-independent methionine synthase (MetE) catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to l-homocysteine to form methionine. Previous studies have shown that the MetE active site coordinates a zinc atom, which is thought to act as a Lewis acid and plays a role in the activation of thiol. Extended X-ray absorption fine structure studies and mutagenesis experiments identified the zinc-binding site in MetE from Escherichia coli.

Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT.

Active transport of substrates across cytoplasmic membranes is of great physiological, medical and pharmaceutical importance. The glycerol-3-phosphate (G3P) transporter (GlpT) of the E. coli inner membrane is a secondary active antiporter from the ubiquitous major facilitator superfamily that couples the import of G3P to the efflux of inorganic phosphate (P(i)) down its concentration gradient.

Docking and homology modeling explain inhibition of the human vesicular glutamate transporters.

As membrane transporter proteins, VGLUT1-3 mediate the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. This function is crucial for exocytosis and the role of glutamate as the major excitatory neurotransmitter in the central nervous system. The three transporters, sharing 76% amino acid sequence identity in humans, are highly homologous but differ in regional expression in the brain.

Homology modeling of the human microsomal glucose 6-phosphate transporter explains the mutations that cause the glycogen storage disease type Ib.

Glycogen storage disease type Ib is caused by mutations in the glucose 6-phosphate transporter (G6PT) in the endoplasmic reticulum membrane in liver and kidney. Twenty-eight missense and two deletion mutations that cause the disease were previously shown to reduce or abolish the transporter's activity. However, the mechanisms by which these mutations impair transport remain unknown.

Diffusion and dynamics of penetratin in different membrane mimicking media.

The interaction between the cell-penetrating peptide (CPP) penetratin and different membrane mimetic environments has been investigated by two different NMR methods: 15N spin relaxation and translational diffusion. Diffusion coefficients were measured for penetratin in neutral and in negatively charged bicelles of different size, in sodium dodecyl sulfate micelles (SDS), and in aqueous solution. The diffusion coefficients were used to estimate the amount of free and bicelle/micelle-bound penetratin and the results revealed that penetratin binds almost fully to all studied membrane mimetics.