Bicyclic enol cyclocarbamates inhibit penicillin-binding proteins.

Natural products form attractive leads for the development of chemical probes and drugs. The antibacterial lipopeptide Brabantamide A contains an unusual enol cyclocarbamate and we used this scaffold as inspiration for the synthesis of a panel of enol cyclocarbamate containing compounds. By equipping the scaffold with different groups, we identified structural features that are essential for antibacterial activity.

LipidII: Just Another Brick in the Wall?

Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow.

In vivo cluster formation of nisin and lipid II is correlated with membrane depolarization.

Nisin and related lantibiotics kill bacteria by pore formation or by sequestering lipid II. Some lantibiotics sequester lipid II into clusters, which were suggested to kill cells through delocalized peptidoglycan synthesis. Here, we show that cluster formation is always concomitant with (i) membrane pore formation and (ii) membrane depolarization.

X-ray structure of the mouse serotonin 5-HT3 receptor.

Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.

Large scale expression and purification of the mouse 5-HT3 receptor.

Receptors of the Cys-loop family are central to neurotransmission and primary therapeutic targets. In order to decipher their gating and modulation mechanisms, structural data is essential. However, structural studies require large amounts of pure, functional receptors.

Thermal unfolding of a mammalian pentameric ligand-gated ion channel proceeds at consecutive, distinct steps.

Pentameric ligand-gated ion channels (LGICs) play an important role in fast synaptic signal transduction. Binding of agonists to the β-sheet-structured extracellular domain opens an ion channel in the transmembrane α-helical region of the LGIC. How the structurally distinct and distant domains are functionally coupled for such central transmembrane signaling processes remains an open question.

Flavin binding to the high affinity riboflavin transporter RibU.

The first biochemical and spectroscopic characterization of a purified membrane transporter for riboflavin (vitamin B(2)) is presented. The riboflavin transporter RibU from the bacterium Lactococcus lactis was overexpressed, solubilized, and purified. The purified transporter was bright yellow when the cells had been cultured in rich medium.