Spatial redistribution of neurosecretory vesicles upon stimulation accelerates their directed transport to the plasma membrane.

Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane.

LAM-1 from Lysobacter antibioticus: A potent zinc-dependent activity that inactivates ß-lactam antibiotics.

Resistance to ß-lactam antibiotics, including the "last-resort" carbapenems, has emerged as a major threat to global health. A major resistance mechanism employed by pathogens involves the use of metallo-ß-lactamases (MBLs), zinc-dependent enzymes that inactivate most of the ß-lactam antibiotics used to treat infections. Variants of MBLs are frequently discovered in clinical environments. However, an increasing number of such enzymes have been identified in microorganisms that are less impacted by human activities. Here, an MBL from Lysobacter antibioticus, isolated from the rhizosphere, has been shown to be highly active toward numerous ß-lactam antibiotics. Its activity is higher than that of some of the most effective MBLs linked to hospital-acquired antibiotic resistance and thus poses an interesting system to investigate evolutionary pressures that drive the emergence of such biocatalysts.

Five-coordinate transition metal complexes and the value of τ5: observations and caveats.

The τ5 parameter, first proposed by Addison and coworkers, is the principal measure of the geometry of five-coordinate transition metal complexes, with τ5 = 0 said to describe a perfect square pyramidal geometry and τ5 = 1 a perfect trigonal pyramidal geometry. Therefore, the geometries of all five-coordinate complexes are assumed to lie on a continuum between these two extremes. Herein we show that there are a significant number of examples of transition metal complexes having τ5 > 1, leading to an equatorially distorted trigonal bipyramidal geometry with the transition metal ion lying out of the plane of the equatorial donor atoms. We also show that complexes having τ5 = 0 and displaying perfect square pyramidal geometry are very much the exception, and that the majority of complexes for which τ5 = 0 have the metal ion sitting above the mean plane of the donor atoms in the square plane, in a basally distorted square pyramidal geometry. Density functional theory computations on a number of these complexes show that the structural distortions are inherent features of the complexes, and not merely the result of intermolecular interactions.