Binding Pockets and Pathways for Dioxygen through the KijD3 N‐Oxygenase in Complex with Flavin Mononucleotide Cofactor and a 3‐Aminoglucose Substrate: Predictions from Molecular Dynamics Simulations

In this work, two protein systems, Kij3D? FMN? AKM? O₂ and Kij3D? FMN? O₂, made of KijD3 N‐oxygenase, flavin mononucleotide (FMN) cofactor, dTDP‐3‐amino‐2,3,6‐trideoxy‐4‐keto‐3‐methyl‐D ‐glucose (AKM) substrate, and dioxygen (O₂), have been assembled by adding a molecule of O₂, and removing (or not) AKM, to crystal data for the Kij3D? FMN? AKM complex. Egress of AKM and O₂ from these systems was then investigated by applying a tiny external random force, in turn, to their center of mass in the course of molecular dynamics in explicit H₂O. It turned out that the wide AKM channel, even when emptied, does not constitute the main route for O₂ egress. Other routes appear to be also viable, while various binding pockets (BPs) outside the active center are prone to trap O₂. By reversing the reasoning, these can also be considered as routes for uptake of O₂ by the protein, before or after AKM uptake, while BPs may serve as reservoirs of O₂. This shows that the small molecule O₂ is capable of permeating the protein by exploiting all nearby interstices that are created on thermal fluctuations of the protein, rather than having necessarily to look for farther, permanent channels.     

Motor function in microgravity: movement in weightlessness

Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.     

Acceleration of climate warming and plant dynamics in Antarctica

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Cheetahs,Acinonyx jubatus,balance turn capacity with pace when chasing prey

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world''s fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s⁻¹ and accelerated up to 7.5 m s⁻² with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.     

The Effects of Organic Solvent on the Ribosyl Transfer Reaction by Thermostable Purine Nucleoside Phosphorylase and Pyrimidine Nucleoside Phosphorylase from Bacillus stearothermophilus JTS 859

The effects of organic solvents on the reaction rate and equilibrium of the ribosyl transfer reaction catalyzed by thermostable purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus JTS 859 were examined at 60°C. The reaction rate in the presence of 10% acetone was 1.6 times higher than that of the control. Acetone was the best organic solvent among those tested for accelerating the reaction rate without denaturing the enzymes. On the other hand, the reaction rate in the presence of 5% ethyl acetate was 1.5 times higher than that of the control. However the enzymes were denatured completely after 1 h incubation. Consequently, the acceleration was not attributed to the stabilization of the enzymes. The equilibrium constants of the reaction were not influenced by the presence of acetone, methyl or ethyl alcohols.     

Polyanion binding accelerates the formation of stable and low‐toxic aggregates of ALS‐linked SOD1 mutant A4V

The toxic property thus far shared by both ALS‐linked SOD1 variants and wild‐type SOD1 is an increased propensity to aggregation. However, whether SOD1 oligomers or aggregates are toxic to cells remains to be well defined. Moreover, how the toxic SOD1 species are removed from intra‐ and extracellular environments also needs to be further explored. The DNA binding has been shown to be capable of accelerating the aggregatio\n of wild‐type and oxidized SOD1 forms under acidic and neutral conditions. In this study, we explore the binding of DNA and heparin, two types of essential life polyanions, to A4V, an ALS‐linked SOD1 mutant, under acidic conditions, and its consequences. The polyanion binding alters the A4V conformation, neutralizes its local positive charges, and increases its local concentrations along the polyanion chain, which are sufficient to lead to acceleration of the pH‐dependent A4V aggregation. The accelerated aggregation, which is ascribed to the polyanion binding‐mediated removal or shortening of the lag phase in aggregation, contributes to the formation of amorphous A4V nanoparticles. The prolonged incubation with polyanions not only results in the complete conversion of likely soluble toxic A4V oligomers into non‐ and low‐toxic SDS‐resistant aggregates, but also increases their stability. Although this is only an initial step toward reducing the toxicity of SOD1 mutants, the accelerating role of polyanions in protein aggregation might become one of the rapid pathways that remove toxic forms of SOD1 mutants from intra‐ and extracellular environments. Proteins 2014; 82:3356–3372. © 2014 Wiley Periodicals, Inc.